name aliases binding partner physiology / oncology references€¦ · amigo1 or amigo3. may...

MMMP Biomap #87

Name Aliases Binding partner Physiology / Oncology References

AJAP1 Adherens junction associated protein 1, SHREW1

? PHY: Expressed in uterus and pancreas. Plays a role in cell adhesion and migration. Forms a complex with CDH1 and beta-catenin at adherens junctions [1]

ONC: Frequently deleted in oligodendrogliomas, functions to inhibit cell adhesion and migration [2]

[1] http://www.uniprot.org/uniprot/Q9UKB5. [2] McDonald JM, Cancer Biol Ther 2006, 5:300-4

ALCAM Activated leukocyte cell adhesion molecule, CD166, MEMD (melanoma metastasis clone D)

CD6 PHY: Adhesion of activated leukocytes and neurons

ONC: Expressed by different tumor types including melanoma; mediates cancer/ melanoma invasiveness [1,2]

[1] Ofori-Acquah SF, Transl Res 2008, 151:122-8. [2] van Kilsdonk JW, Cancer Res 2008, 68:3671-9

AMICA1 Adhesion molecule interacting with CXADR antigen 1, JAML (junctional adhesion molecule-like)

CXADR PHY: Expression is restricted to the hematopoietic tissues with the exception of liver. May function in transmigration of leukocytes through epithelial and endothelial tissues. Mediates adhesive interactions with CXADR, a protein of the junctional complex of epithelial cells [1]

ONC: Enhances myeloid leukemia cell adhesion to endothelial cells [2]

[1] http://www.uniprot.org/uniprot/Q86YT9. [2] Moog-Lutz C, Blood 2003, 102:3371-8

AMIGO1 Amphoterin-induced gene and open reading frame 1, Alivin-2

AMIGO PHY: May be involved in fasciculation as well as myelination of developing neural axons. May have a role in regeneration as well as neural plasticity in the adult nervous system. May mediate homophilic as well as heterophilic cell-cell interaction and contribute to signal transduction through its intracellular domain [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q86WK6

AMIGO2 Amphoterin-induced gene and open reading frame 2, DEGA (Differentially expressed in gastric adenocarcinomas)

AMIGO PHY: Highest levels in breast, ovary, cervix, and uterus. May mediate homophilic as well as heterophilic cell-cell interaction with

[1] http://www.uniprot.org/uniprot/Q86SJ2. [2] Rabenau KE, Oncogene 2004, 23:5056-67

MMMP Biomap #87

AMIGO1 or AMIGO3. May contribute to signal transduction through its intracellular domain [1]

ONC: High expression in 45% of gastric adenocarcinomas; stable expression of an antisense construct in a gastric adenocarcinoma cell line leads to increased ploidy, chromosomal instability, decreased cell adhesion/ migration and nearly complete abrogation of tumorigenicity in nude mice [2]

AMIGO3 Amphoterin-induced gene and open reading frame 3

AMIGO PHY: May mediate heterophilic cell-cell interaction. May contribute to signal transduction through its intracellular domain [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q86WK7

BCAM Basal cell adhesion molecule, CD239, Lutheran blood group antigen

Laminins (?) PHY: Associated with basal layer of epithelial and endothelial cells

ONC: Mediates adhesion of hepatocellular carcinoma (HCC) cells to laminin alpha 5 [1]

[1] Kikkawa Y, Exp Cell Res 2008, 314:2579-90

CADM1 Cell adhesion molecule 1, TSLC1 (tumor suppressor in lung cancer), IGSF4, SYNCAM1

CADM1 CADM3 PVRL3

PHY: Calcium-independent homophilic and heterophilic cell-cell adhesion

ONC: Considered a tumor suppressor gene [1], especially for neuroblastoma [2] and lung cancer [3]

[1] Murakami Y, Cancer Sci 2005, 96:543-52. [2] Nowacki S, Oncogene 2008, 27:3329-38. [3] Kikuchi S, Cancer 2006, 106:1751-8

CADM2 Cell adhesion molecule 2, NECL3, SYNCAM2

? PHY: ?

ONC: -

[1] http://www.uniprot.org/uniprot/Q8N3J6

CADM3 Cell adhesion molecule 3, IGSF4B, TSLL1 (TSLC1-like 1), NECL1, SYNCAM3

CADM3 IGSF4 PVRL1 PVRL3

PHY: Calcium-independent homophilic and heterophilic cell-cell adhesion activity

ONC: Possibly involved in cancer biology (CADM1 homologous) [1]

[1] Fukuhara H, Oncogene 2001, 20:5401-7

CADM4 Cell adhesion molecule 4, IGSF4C, TSLL2 (TSLC1-like 2), NECL4, SYNCAM4

? PHY: Calcium- and magnesium-independent cell-cell adhesion activity

ONC: Possibly involved in cancer biology

[1] Fukuhara H, Oncogene 2001, 20:5401-7

MMMP Biomap #87

(CADM1 homologous) [1]

CD2 CD2 antigen p50, LFA-2, LFA-3 receptor, rosette receptor, T-cell surface antigen T11/Leu-5

LFA-3 CD48

PHY: CD2 interacts with lymphocyte function-associated antigen (LFA-3) and CD48 to mediate adhesion between T-cells and other cell types. CD2 is implicated in the triggering of T-cells, the cytoplasmic domain is implicated in the signaling function

ONC: CD2 (and CD36) expression has an adverse prognostic impact in adult de novo acute myeloid leukemia (AML) patients [2]

[1] http://www.uniprot.org/uniprot/P06729. [2] Perea G, Leuk Res 2005, 29:1109-16

CD4 CD4 antigen p55, T-cell surface antigen T4/Leu-3

MHC class II PHY: Identifies helper T cells (HTL) and suppressor/ regulatory T cells (Treg) that interact with MHC class II bearing targets. Singaling and adhesion coreceptor in class II restricted antigen-induced T cell activation. Primary receptor for HIV virus [1]

ONC: -

[1] http://www.uniprot.org/uniprot/P01730

CD6 Tp120 CD166 PHY: Expressed by thymocytes, mature T-cells, a subset of B-cells known as B-1 cells, and by some cells in the brain. After T-cell activation, becomes phosphorylated on Ser, Thr and Tyr residues [1]

ONC: -


CD8a CD8 alpha (p32), T-lymphocyte differentiation antigen T8/Leu-2

MHC class I PHY: Identifies cytotoxic T cells (CTL) and suppressor/ regulatory T cells (Treg) that interact with MHC class I bearing targets. Signaling and adhesion coreceptor in class II restricted antigen-induced T cell activation. In general heterodimer of an alpha and a beta chain [2]

ONC: -

[1] Smith TR, Trends Immunol 2008, 29:337-42. [2] http://www.uniprot.org/uniprot/P01732

CD8b CD8 beta (p37), T-cell surface glycoprotein CD8 beta chain

MHC class I PHY: Identifies cytotoxic T cells (CTL) and suppressor/ regulatory T cells (Treg) that interact with MHC class I bearing targets. Signaling and adhesion coreceptor in class II restricted antigen-induced T cell activation. In general heterodimer of an alpha and a beta

[1] Smith TR, Trends Immunol 2008, 29:337-42. [2] http://www.uniprot.org/uniprot/P10966

MMMP Biomap #87

chain [2]

ONC: -

CD9 Tetraspanin-29, Leukocyte antigen MIC3 ? PHY: Involved in platelet activation and aggregation. Regulates paranodal junction formation. Required for gamete fusion. Involved in cell adhesion and motility. Expressed by a variety of hematopoietic and epithelial cells [1]. CD9 (and CD81) associate with phosphatidyl inositol 4-kinase (PI4K), which locally produces phosphoinositides (such as phosphatidylinositol-4,5-bisphosphate; this causes the recruitment and activation of SHC (SRC-homology-2-domain-containing transforming protein): subsequent RAS-mediated activation of ERK or p38MAPK or JNK pathways leads to proliferation or apoptosis, respectively [8]

ONC: Suppresses cell motility and in vivo metastasis of mouse melanoma [2,3]. CD9 may act as a metastasis suppressor, at least in part, by neutralizing Aggrus-mediated platelet aggregation [4]. In multiple myeloma, CD9 is epigenetically silenced during disease progression and correlates with survival [5]. However, anti-CD9 antibodies inhibit transendothelial migration of melanoma cells [6]; plus, CD9 induces MMP-2 expression by activating c- Jun through p38 MAPK and JNK signaling pathways in human melanoma cells [7]

[1] http://www.uniprot.org/uniprot/P21926. [2] Ikeyama S, J Exp Med 1993, 177:1231-7. [3] Miyake M, Oncogene 2000, 19:5221-6. [4] Nakazawa Y, Blood 2008, 112:1730-9. [5] De Bruyne E, Clin Cancer Res 2008, 14:2918-26. [6] Longo N, Blood 2001, 98:3717-26. [7] Hong IK, Exp Mol Med 2005, 37:230-9. [8] Hemler ME, Nat Rev Mol Cell Biol 2005, 6:801-11

CD33 CD33 antigen (gp67), SIGLEC3 (Sialic acid-binding Ig-like lectin 3), sialoadhesin

Sialic acid containing proteins

PHY: Putative adhesion molecule of myelomonocytic-derived cells that mediates sialic-acid dependent binding to cells. Contains 2 copies of a cytoplasmic immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. In the immune response, may act as an inhibitory receptor upon ligand-induced tyrosine phosphorylation

[1] http://www.uniprot.org/uniprot/P20138. [2] Stasi R, Expert Opin Biol Ther 2008, 8:527-40

MMMP Biomap #87

by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules [1]

ONC: Is used as a therapeutic target for acute myeloid leukemia [2]

CD34 - L-selectin PHY: Adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Selectively expressed on hematopoietic progenitor cells and the small vessel endothelium of a variety of tissues [1]

ONC: -


CD36 GP3B, PAS-4, Platelet collagen receptor, Thrombospondin receptor, Fatty acid translocase

Collagen Thrombospondin

PHY: Expressed by platelets, macrophages and microvascular endothelial cells. Scavenger receptor for oxidized LDL. Platelet adhesion. Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes. Defects in CD36 are the cause of platelet glycoprotein IV deficiency [1]

ONC: The ability of metronomic chemotherapy to induce endothelial apoptosis has been traced to increased endothelial expression of thrombospondin-1, which activates endothelial CD36 receptors, triggering the extrinsic apoptotic pathway [2]

[1] http://www.uniprot.org/uniprot/P16671. [2] McCarty MF, Med Hypotheses 2008, 70:419-23

CD42a GP9, GPIX (glycoprotein IX, platelet) Von Willebrand factor PHY: The heteromeric complex of CD42 proteins functions as the vWF receptor and mediates vWF-dependent platelet adhesion to blood vessels. The adhesion of platelets to injured vascular surfaces in the arterial circulation is a critical initiating event in hemostasis. Defects in GP9 are a cause of Bernard-Soulier syndrome (BSS) or giant platelet disease (GPD) [1]

ONC: -


MMMP Biomap #87

CD42b GP1BA (glycoprotein Ib alpha polypeptide, platelet), CD42b alpha, glycocalicin

Von Willebrand factor PHY: Acts as a heterodimer composed of GP-Ib alpha and beta. See CD42a for more details [1]

ONC: -


CD42c GP1BB (glycoprotein Ib beta polypeptide, platelet), CD42b beta

Von Willebrand factor PHY: Acts as a heterodimer composed of GP-Ib alpha and beta. See CD42a for more details [1]

ONC: -


CD42d GP5 (glycoprotein V, platelet) Von Willebrand factor PHY: Acts as a heterodimer composed of GP-Ib alpha and beta. See CD42a for more details [1]

ONC: -


CD43 Sialophorin (SPN), leukosialin (LSN), GPL115, Galactoglycoprotein (GALGP)

Selectins PHY: This sialomucin is one of the major glycoproteins of thymocytes and T lymphocytes. Plays a role in the physicochemical properties of the T-cell surface and in lectin binding. This sialic acid rich protein presents carbohydrate ligands to selectins. Is a counter receptor for SN/SIGLEC-1. May inhibit ICAM-1 (CD54)-LFA-1 (CD11A/CD18) interaction. During T-cell activation is actively removed from the T-cell/antigen-presenting cell (APC) contact site thus suggesting a negative regulatory role in adaptive immune response [1]. Overall, can have both pro- and anti-adhesive properties [2]

ONC: -

[1] http://www.uniprot.org/uniprot/P16150. [2] Matsumoto M, J Immunol 2008, 181:3628-35

CD44 Indian blood group, MIC4, MDU2, MDU3, CD44R, HCELL (hematopoietic cell E- and L-selectin ligand), CSPG8 (chondroitin sulfate proteoglycan 8), MC56, Pgp1 (phagocytic glycoprotein I)

Hyaluronic acid Selectin-E Selectin-L Selectin-P Collagen Laminin Fibronectin

PHY: Mediates cell-cell and cell-matrix interactions through its affinity for a number of ligands such as hyaluronic acid (and other glycosamino glycans) [1], osteopontin, collagens, and matrix metalloproteinases (MMP). Also involved in lymphocyte activation, recirculation and homing, and in hematopoiesis. Altered expression or dysfunction causes numerous pathogenic

[1] Heldin P, Connect Tissue Res 2008, 49:215-8. [2] Naor D, Semin Cancer Biol 2008, 18:260-7. [3] Ahrens T, J Invest Dermatol 2001, 116:93-101. [4] Bourguignon LY, Semin Cancer Biol 2008, 18:251-9. [5] Anderegg U, J Invest Dermatol 2008, Epub ahead of print. [6] http://www.uniprot.org/uniprot/P16070

MMMP Biomap #87

phenotypes. Great protein heterogeneity due to numerous alternative splicing and post-translational modification events. Responsible for the Indian blood group system [6]

ONC: Interaction with hyaluronate plays an important role in cell migration, tumor growth and progression [2]. Expressed on many tumor types, supports cell migration and transmits survival signals, thereby being pro-oncogenic in many tumor models [2], including melanoma [3]. By activating RhoGTPase signaling, it leads to cytoskeleton reorganization and AKT activation, which in turn promote cell migration and survival, respectively [4]. Soluble CD44 (produced by ADAM10 sheddase activity) can abolish the cell proliferation-promoting effect of hyaluronate on melanoma cells [5]

CD48 BLAST, BCM1, SLAMF2, B-lymphocyte activation marker, OX-45, Lym-3

CD2 PHY: Ligand for CD2, might facilitate interaction between activated lymphocytes. Probably involved in regulating T-cell activation

ONC: -


CD58 LFA-3 (lymphocyte function associated 3)

CD2 PHY: Ligand of the T-lymphocyte CD2 glycoprotein: this interaction is important in mediating thymocyte interactions with thymic epithelial cells and antigen-independent and -dependent interactions of T-lymphocytes with target cells and antigen-presenting cells (T cell activation) [1]

ONC: Potentially useful in the diagnosis and monitoring of precursor B-cell acute lymphoblastic leukemia (B-ALL), but only when blasts express high levels of CD58 [2]

[1] http://www.uniprot.org/uniprot/P19256. [2] Lee RV, Am J Clin Pathol 2005, 123:119-24

CD68 Macrosialin, GP110, SCARD1 (scavenger receptor class D member 1)

Selectins Lectins

PHY: Highly expressed by blood monocytes and tissue macrophages. Bind to tissue- and organ-specific lectins or selectins, allowing homing of macrophage subsets to particular

[1] http://www.uniprot.org/uniprot/P34810. [2] Mäkitie T, Invest Ophthalmol Vis Sci 2001, 42:1414-21. [3] Piras F, Cancer 2005, 104:1246-54

MMMP Biomap #87

sites [1]

ONC: Expressed in many tumor cell lines which could allow them to attach to selectins on vascular endothelium, facilitating their dissemination to secondary sites [1]. Tumor infiltrating macrophages (TIM) identified as CD68 positive cells are associated with the prognosis of uveal [2] but not skin [3] melanoma

CD151 Tetraspanin 24, PETA-3, SFA-1 ITG alpha3-beta1 ITG alpha5-beta1 ITG alpha3-beta1 ITG alpha6-beta4 CD9 CD181

PHY: Essential for the proper assembly of the glomerular and tubular basement membranes in kidney. Expressed in a variety of tissues including vascular endothelium and epidermis. Defines the MER2=RAPH1 antigen of the RAPH blood group system. Defects in CD151 are the cause of nephropathy with pretibial epidermolysis bullosa and deafness (NPEBD) [1]

ONC: Regulation of CD151 by hypoxia controls cell adhesion and metastasis in colorectal cancer [2]. CD151 accelerates breast cancer by regulating alpha 6 integrin function, signaling, and molecular organization [3]. However, loss of cancer cell migration in vivo is the result of enhanced tumor cell-matrix interactions promoted by CD151, which prevent dissociation by individual cells and leads to a subsequent inhibition of invasion and intravasation at the site of the primary tumor [4]

[1] http://www.uniprot.org/uniprot/P48509. [2] Chien CW, Clin Cancer Res 2008, 14:8043-51. [3] Yang XH, Cancer Res 2008, 68:3204-13. [4] Zijlstra A, Cancer Cell 2008, 13:221-34

CD164 Sialomucin, MUC24, endolyn ? PHY: Involved in cell adhesion and migration. Forms complexes with the motility-stimulating chemokine receptor CXCR4 in response to the CXCR4 ligand, CXCL12/SDF1 [1]

ONC: May participate in the homing of prostate cancer cells to the bone marrow [2]. Expressed in small intestine, colon, lung, thyroid and in colorectal and pancreatic adenocarcinoma [3]

[1] Forde S, Blood 2007, 109:1825-33. [2] Havens AM, BMC Cancer 2006, 6:195. [3] http://www.uniprot.org/uniprot/Q04900

MMMP Biomap #87

CD209 CD-SIGN1 (Dendritic cell-specific ICAM-3-grabbing non-integrin 1), C-type lectin domain family 4 member L

ICAM1 ICAM2 ICAM3

PHY: Mainly expressed on dendritic cells (DC). May act as a DC rolling receptor that mediates transendothelial migration of DC from blood to tissues. Seems to regulate DC-induced T cell proliferation by binding to ICAM3 on T cells in the immunological synapse formed between DC and T cells. Pathogen-recognition receptor expressed on the surface of immature DC and involved in initiation of primary immune response [1] ONC: -

[1] http://www.uniprot.org/uniprot/Q9NNX6

CD226 DNAM1 (DNAX accessory molecule 1) CD112 CD155

PHY: Receptor involved in intercellular adhesion, lymphocyte signaling, cytotoxicity and lymphokine secretion mediated by cytotoxic T-lymphocyte (CTL) and NK cell [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q15762

CD229 LY9, T-lymphocyte surface antigen Ly-9 CD229 (?) PHY: May participate in adhesion reactions between T lymphocytes and accessory cells by homophilic interaction [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9HBG7

CD248 Endosialin, TEM1 (tumor endothelial marker 1)

MAC-2 PHY: Interaction of endosialin/TEM1 with extracellular matrix proteins mediates cell adhesion and migration [1]

ONC: Is expressed in stromal cells, endothelial cells, and pericytes within various tumors, as well as by some malignant cells [2]. Is a binding partner of metastasis-related protein Mac-2 BP/90K (extracellular ligand) [3]

[1] Tomkowicz B, Proc Natl Acad Sci USA 2007, 104:17965-70. [2] Rouleau C, Clin Cancer Res 2008, 14:7223-36. [3] Becker R, FASEB J 2008, 22:3059-67

MMMP Biomap #87

CDH1 E-cadherin (epithelial), Cadherin 1, uvomorulin, CD324

CDH1 ITG alphaE-beta7

PHY: Acts as a homodimer. Involved in cell-cell adhesion, mobility and proliferation of epithelial cells. The cytoplasmic domain interacts with beta-catenin to form the cadherin/catenin adhesion complex (adherens junction, see below Figure), which connects to the actin skeleton through alpha-catenin

ONC: Is believed to act as a tumor suppressor gene (TSG) in different types of carcinoma, mainly by favoring cell adhesion/polarity, preventing beta-catenin from translocation to the nucleus and inhibiting mitogenic signaling through its interaction with growth factor receptors [1-3]. Loss of E-cadherin and acquisition of N-cadherin expression (the "cadherin switch") is a hallmark of epithelial-mesenchymal transition (EMT), a key event in cancer progression/ invasiveness [4]. CDH1 loss promotes melanoma progression in preclinical models [5-8] and is associated with worse prognosis of patients with melanoma [9]

CADHERINS (CDHs)

The cadherin superfamily of cell-cell adhesion proteins includes classical cadherins (CDH), protocadherins (PCDH) and atypical cadherins (FAT, Dachsous, and Flamingo cadherins). CDHs are single-pass transmembrane, calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. Besides their adhesive properties, cadherins may act by transferring intracellular signals through interaction with a complex network of cytoskeletal and signaling molecules. They may signal in different ways: through direct activation of signaling pathways, through interaction with cell-specific growth factor receptors or by controlling the translocation to the nucleus of beta-catenin and other transcription factors. Cadherins play pivotal roles in important morphogenetic and differentiation processes during development, and in maintaining tissue integrity and homeostasis. Changes in cadherin expression throughout development enable differentiation and the formation of various organs. In addition to these functions, cadherins have strong implications in carcinogenesis, as exemplified by the fact that frequently tumor cells show deregulated cadherin expression and inappropriate switching among family members. REFERENCES: [1] Pokutta S, Annu Rev Cell Dev Biol 2007, 23:237-61. [2] Stemmler MP, Mol Biosyst 2008, 4:835-50. [3] Suzuki SC, Dev Growth Differ 2008, 50 Suppl 1:S119-30

[1] Jeanes A, Oncogene 2008, 27:6920-9. [2] Cavallaro U, Nat Rev Cancer 2004, 4:118-32. [3] Stemmler MP, Mol Biosyst 2008, 4:835-50. [4] Mariotti A, Expert Opin Investig Drugs 2007, 16:451-65. [5] Rodriguez M, Cancer Res 2008, 68:7872-81. [6] Smit DJ, Int J Cancer 2007, 121:2653-60. [7] Kippenberger S, Melanoma Res 2006, 16:393-403. [8] Robert G, Cancer Res 2006, 66:7516-23. [9] Kreizenbeck GM, Cancer Epidemiol Biomarkers Prev 2008, 17:949-58

MMMP Biomap #87

CDH2 N-cadherin (neuronal), Cadherin 2, CDHN, CD325

CDH2

PHY: Plays a key role in cell migration. In embryogenesis, N-cadherin is the key molecule during gastrulation and neural crest development. N-cadherin mediated contacts activate several pathways like Rho GTPases and function in tyrosine kinase signaling, with special regard to the fibroblast growth factor receptor (FGFR) pathway [1,2]

ONC: Is believed to act as an oncogene in different tumor types, mainly by favoring malignant cell motility, migration and invasiveness [3]. Loss of E-cadherin and acquisition of N-cadherin expression (the "cadherin switch") is a hallmark of epithelial-mesenchymal transition (EMT), a key event in cancer progression/ invasiveness [4]. Several lines of evidence suggest that CDH2 plays a significant role also in melanoma progression/ aggressiveness in preclinical models [5-8]

[1] Derycke LD, Int J Dev Biol 2004, 48:463-76. [2] Hansen SM, Cell Mol Life Sci 2008, 65:3809-21. [3] Cavallaro U, Curr Opin Investig Drugs 2004, 5:1274-8. [4] Mariotti A, Expert Opin Investig Drugs 2007, 16:451-65. [5] Augustine CK, Cancer Res 2008, 68:3777-84. [6] Watson-Hurst K, Cancer Biol Ther 2006, 5:1375-82. [7] Liu ZJ, Cancer Res 2006, 66:4182-90. [8] Kuphal S, Oncogene 2006, 25:248-59

CDH3 P-cadherin (placental), Cadherin 3, CDHP, PCAD

CDH3 PHY: Defects in CDH3 are the cause of hypotrichosis with juvenile macular dystrophy (HJMD) and ectodermal dysplasia with ectrodactyly and macular dystrophy (EEM) [1]

ONC: Considered a novel tumor-associated antigen (TAA) and thus a possible target for immunotherapy for different carcinomas [2]. Usually associated with worse prognosis in patients with carcinomas [3,4], while in patients with melanoma the findings are conflicting [6-8]

[1] http://www.uniprot.org/uniprot/P22223. [2] Imai K, Clin Cancer Res 2008, 14:6487-95. [3] Bryan RT, J Pathol 2008, 215:184-94. [4] Gravdal K, Clin Cancer Res 2007, 13:7003-11. [5] Paredes J, Breast Cancer Res 2007, 9:214. [6] Kreizenbeck GM, Cancer Epidemiol Biomarkers Prev 2008, 17:949-58. [7] Bauer R, J Clin Pathol 2006, 59:699-705. [8] Bachmann IM, Clin Cancer Res 2005, 11(24 Pt 1):8606-14

CDH4 R-cadherin (retinal), Cadherin 4 CDH4 PHY: Expressed mainly in brain but also found in other tissues [1]

ONC: Inhibits myogenesis and induces myoblast transformation via Rac1 GTPase [2].

[1] http://www.uniprot.org/uniprot/P55283. [2] Kucharczak J, Cancer Res 2008, 68:6559-68. [3] Miotto E, Cancer Res 2004, 64:8156-9

MMMP Biomap #87

On the other hand, frequent aberrant methylation of the CDH4 gene promoter in human colorectal and gastric cancer makes it a candidate tumor suppressor gene [3]

CDH5 VE-cadherin (vascular endothelial), Cadherin 5, CD144

CDH5 PHY: Plays an important role in endothelial cell biology (with special regard to angiogenesis) through control of the organization of intercellular junctions. Associates with alpha-catenin forming a link to the cytoskeleton. Mainly expressed in endothelial tissues and brain. In vascular endothelium, adherens junctions between endothelial cells are composed of VE-cadherin, which is crucial for the proper assembly of vascular structures and control of vascular permeability and leukocyte diapedesis [1,2]

ONC: Tumor-induced upregulation of TWIST, SNAIL and SLUG represses the activity of the human VE-cadherin promoter [3]. Tumor necrosis factor-alpha (TNF) damages tumor blood vessel integrity by targeting VE-cadherin [4]. VE-cadherin regulates EphA2 in aggressive melanoma cells with implications for vasculogenic mimicry [5]. Neovessels in tumor grafts and Matrigel implants harbor strong staining, indicating that promoter activity is enhanced in angiogenic situations [6]

[1] Taveau JC, Biochem Soc Trans 2008, 36(Pt 2):189-93. [2] Dejana E, J Cell Sci 2008, 121(Pt 13):2115-22. [3] Lopez D, Arch Biochem Biophys 2008, Epub ahead of print. [4] Menon C, Ann Surg 2006, 244:781-91. [5] Hess AR, Cancer Biol Ther 2006, 5:228-33. [6] Prandini MH, Oncogene 2005, 24:2992-3001

CDH6 K-cadherin (kidney), Cadherin 6 CDH6 PHY: Highly expressed in brain, cerebellum, and kidney. Lung, pancreas, and gastric mucosa show a weak expression [1]

ONC: Expressed in kidney carcinoma [2]

[1] http://www.uniprot.org/uniprot/P55285. [2] Xiang YY, Cancer Res 1994, 54:3034-41

CDH7 Cadherin 7, CDH7L1 CDH7 PHY: -

ONC: Might play a role in melanocyte transformation: the majority of the tested malignant melanoma cell lines produce N-cadherin and/or cadherin-7 whereas melanocyte cell lines do not (the converse

[1] Moore R, Oncogene 2004, 23:6726-35. [2] Winklmeier A, Cancer Sci 2009, 100:261-8

MMMP Biomap #87

was observed for E-cadherin) [1]. In contrast, CDH7 - which binds to melanoma migration promoting molecule MIA - is upregulated in metastatic as compared to primary melanomas and its forced overexpression inhibits metastatic melanoma cell migration [2]

CDH8 Cadherin 8 CDH8 PHY: Mainly expressed in brain. Found in certain nerve cell lines, such as retinoblasts, glioma cells and neuroblasts [1]

ONC: Belongs to a gene expression signature that predicts survival of patients with non-small cell lung cancer (NSCLC) [2]

[1] http://www.uniprot.org/uniprot/P55286. [2] Lu Y, PLoS Med 2006, 3(12):e467

CDH9 Cadherin 9, T1-cadherin CDH9 PHY: ?

ONC: -

-

CDH10 Cadherin 10, T2-cadherin CDH10 PHY: Predominantly expressed in brain. Also found in adult and fetal kidney [1]

ONC: Is a marker for human prostate luminal epithelial cells while is not expressed in prostate cancer [2]

[1] http://www.uniprot.org/uniprot/Q9Y6N8. [2] Walker MM, Mod Pathol 2008, 21:85-95

CDH11 OB-cadherin (osteoblast), Cadherin 11 CDH11 PHY: Expressed mainly in brain but also found in other tissues/cells (e.g. osteoblasts)

ONC: Its expression is associated with survival in patients with osteosarcoma [1]

[1] Nakajima G, Cancer Genomics Proteomics 2008, 5:37-42

CDH12 Cadherin 12, N-cadherin 2 (brain) CDH12 PHY: Mainly expressed in brain [1]

ONC: -


CDH13 H-cadherin (heart), Cadherin 13 CDH13 PHY: Highly expressed in heart. In the CNS, expressed in cerebral cortex, medulla, hippocampus, amygdala, thalamus and substantia nigra. May act as a negative regulator of neural cell growth [1]

ONC: Promoter hypermethylation of CDH13 is found in esophageal adenocarcinoma [2], endometrial carcinoma [3], non small cell lung

[1] http://www.uniprot.org/uniprot/P55290. [2] Jin Z, Int J Cancer 2008, 123:2331-6. [3] Suehiro Y, Clin Cancer Res 2008, 14:3354-61. [4] Feng Q, Cancer Epidemiol Biomarkers Prev 2008, 17:645-54. [5] Thomas G, Nat Genet 2008, 40:310-5

MMMP Biomap #87

carcinoma [4]. Also associated (recessive model) with prostate cancer risk [5]

CDH15 M-cadherin (myotubule), Cadherin 15, CDH14

CDH15 PHY: M-cadherin is part of the myogenic program and may provide a trigger for terminal muscle differentiation [1]

ONC: Its promoter is found methylated in hepatocellular carcinoma (HCC), which correlates with poor prognosis [2]

[1] http://www.uniprot.org/uniprot/P55291. [2] Yamada S, Anticancer Res 2007, 27(4B):2269-74

CDH16 KSP-cadherin (kidney specific), Cadherin 16

CDH16 PHY: Mainly expressed in kidney

ONC: Downregulated in renal cell carcinoma [1]

[1] Thedieck C, Br J Cancer. 2005 Jun 6;92(11):2010-7

CDH17 LI-cadherin (liver, intestine), Cadherin 17 CDH17 PHY: May have a role in the morphological organization of liver and intestine

ONC: Conflicting results on its association with prognosis of gastrointestinal carcinomas [1-3]

[1] Kwak JM, Dis Colon Rectum 2007, 50:1873-80. [2] Dong W, Dig Dis Sci 2007, 52:536-42. [3] Park SS, Ann Surg Oncol 2007, 14:94-9. [4] Ito R, Virchows Arch 2005, 447:717-22

CDH18 Cadherin 18, EY-cadherin, CDH14 CDH18 PHY: ?

ONC: -

-

CDH19 Cadherin 19, CDH7L2 CDH19 PHY: Expressed in many tissues, with the exception of uterus [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9H159

CDH20 Cadherin 20, CDH7L3 CDH20 PHY: Expressed in placenta, adult brain, and fetal brain [1]

ONC: Might play a role in melanocyte transformation: the majority of the tested malignant melanoma cell lines produced N-cadherin and/or cadherin-20 whereas melanocyte cell lines did not (the converse was observed for E-cadherin) [2]

[1] http://www.uniprot.org/uniprot/Q9HBT6. [2] Moore R, Oncogene 2004, 23:6726-35

CDH22 PB-cadherin (pituitary, brain), Cadherin 22

CDH22 PHY: May have a role in the morphological organization of pituitary gland and brain tissues [1]

[1] http://www.uniprot.org/uniprot/Q9UJ99

MMMP Biomap #87

ONC: -

CDH23 Cadherin 23, Otocadherin CDH23 PHY: Organization of the stereocilia bundle of hair cells in the cochlea and the vestibule during embryonic development. Particularly strong expression in the retina. Defects in CDH23 are the cause of Usher syndrome (association of retinitis pigmentosa and sensorineural deafness) [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9H251

CDH24 Cadherin 24, CDH11L CDH24 PHY: ?

ONC: -

-

CDH26 Cadherin 26, VR20 CDH26 PHY: ?

ONC: -

-

CDH29 Cadherin 29 ? PHY: ?

ONC: -

-

CEACAM1 Carcinoembryonic antigen-related cell adhesion molecule 1, BGP (biliary glycoprotein), CD66a

? PHY: ?

ONC: Conflicting findings on non-melanoma tumors [1,2]. Protects melanoma from immune attack [3] and increases melanoma invasiveness [4]

[1] Luo W, Oncogene 1997, 14:1697-704. [2] Gaur S, Mol Cancer 2008, 7:46. [3] Markel G, Immunology 2008, Epub ahead of print. [4] Ebrahimnejad A, Am J Pathol 2004, 165:1781-7

CEACAM3 Carcinoembryonic antigen-related cell adhesion molecule 3, CGM1 (CEA gene family member 1), CD66d

? PHY: Major granulocyte receptor for microorganism recognition and phagocytosis

ONC: Cytosolic domain interacts with S100A9, a putative tumor suppressor protein [1]

[1] Salama I, Eur J Surg Oncol 2008, 34:357-64

CEACAM4 Carcinoembryonic antigen-related cell adhesion molecule 4, CGM7 (CEA gene family member 7)

? PHY: Mainly expressed by granulocytes

ONC: -

-

CEACAM5 Carcinoembryonic antigen-related cell adhesion molecule 5, CEA, CD66e

Selectin-E [1] Selectin-L [1]

PHY: Found in fetal colon and in GI (gastrointestinal) adenocarcinomas

ONC: Routinely used as serum marker for GI carcinomas. Is not expressed by human melanoma cell lines [2]

[1] Thomas SN, J Biol Chem 2008, 283:15647-55. [2] Ravindranath MH, Anticancer Res 2000, 20:3083-92

MMMP Biomap #87

CEACAM6 Carcinoembryonic antigen-related cell adhesion molecule 6, NCA, CD66c

? PHY: ?

ONC: Overexpressed in a variety of epithelial cancers, promotes tumor invasiveness [1]. Is a TGF-beta/SMAD3 target [2]

[1] Han SU, Oncogene 2008, 27:675-83. [2] Ordonez C, J Cell Physiol 2007, 210:757-65

CEACAM7 Carcinoembryonic antigen-related cell adhesion molecule 7, CGM2 (CEA gene family member 2)

? PHY: Expressed by normal colon epithelial cells

ONC: Downregulated in colon [1] and upregulated in gastric carcinoma cells [2]

[1] Thompson J, Cancer Res 1997, 57:1776-84. [2] Kinugasa T, Int J Cancer 1998, 76:148-53

CEACAM8 Carcinoembryonic antigen-related cell adhesion molecule 8, CGM6 (CEA gene family member 6), CD66b

? PHY: Expressed by leukocytes of normal bone marrow

ONC: Expressed by leukemia cells [1,2]

[1] Berling B, Cancer Res 1990, 50:6534-9. [2] Lasa A, Ann Hematol 2008, 87:205-11

CEACAM16 Carcinoembryonic antigen-related cell adhesion molecule 16

? PHY: ?

ONC: -

[1] Zebhauser R, Genomics 2005, 86:566-80


? PHY: ?

ONC: -


CEACAM19 Carcinoembryonic antigen-related cell adhesion molecule 19, CEAL1

? PHY: ?

ONC: -

-


? PHY: ?

ONC: -



? PHY: ?

ONC: -

-

CHL1 Cell adhesion molecule homologous to L1CAM, CALL, L1CAM2

L1CAM ITG alpha1-beta1 ITG alpha2-beta1

PHY: Involved in nervous system development. Cleaved by metalloprotease ADAM8. Recruits ANK3 to plasma membrane

ONC: Candidate tumor suppressor gene for esophageal carcinoma [1] and uveal melanoma [2]

[1] Qin YR, Int J Cancer 2008, 123:826-30. [2] Tschentscher F, Cancer Res 2003, 63:2578-84

Claudin 1 CLDN1, SEMP1 (senescence-associated epithelial membrane protein 1), ILVASC

Claudins TJP1

PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions.

[1] http://www.uniprot.org/uniprot/O95832. [2] Harten SK, Mol Biol Cell 2008, Epub ahead of print. [3] Chao YC, Am J Respir Crit Care Med

MMMP Biomap #87

TJP2 TJP3

Strongly expressed in liver and kidney. Expressed in heart, brain, spleen, lung and testis. Co-receptor for HCV entry. Defects in CLDN1 are the cause of neonatal ichthyosis-sclerosing cholangitis syndrome (NISCH) also called ichthyosis with leukocyte vacuoles alopecia and sclerosing cholangitis (ILVASC) [1]

ONC: Conflicting data. In renal cell carcinoma (RCC), VHL loss leads to epithelial mesenchymal transition (EMT) by downregulation not only of E-cadherin expression (adherens junction) but also occludin and claudin-1 (tight junction) [2]. Plus, claudin-1 is a metastasis suppressor and correlates with favorable clinical outcome of patients with lung adenocarcinoma [3]. However, claudin-1 overexpression increases invasion and is associated with aggressive histological features in oral squamous cell carcinoma [4], and is an independent negative prognosticator for patients with clear cell renal cell carcinoma [5]. In melanoma, claudin-1 overexpression is enhanced by PKC and contributes to cell motility [6], but loss of claudin-1 expression in melanoma-associated vessels correlates with acquisition of metastatic phenotype [7]

2008, Epub ahead of print. [4] Dos Reis PP, Cancer 2008, 113:3169-80. [5] Fritzsche FR, Clin Cancer Res 2008, 14:7035-42. [6] Leotlela PD, Oncogene 2007, 26:3846-56. [7] Cohn ML, J Cutan Pathol 2005, 32:533-6

Claudin 2 CLDN2 Claudins TJP1 TJP2 TJP3

PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions

ONC: Conflicting data. Downregulation of claudin-2 in breast carcinomas is associated with advanced disease [1]. However, claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation [2]; plus, inhibition of claudin-2 expression by NSAID contributes to NSAID-dependent inhibition of invasion of cancer cells in vitro [3]

[1] Kim TH, Histopathology 2008, 53:48-55. [2] Weber CR, Lab Invest 2008, 88:1110-20. [3] Mima S, Carcinogenesis 2008, 29:1994-2000

MMMP Biomap #87

Claudin 3 CLDN3, CPER2 (Clostridium perfringens enterotoxin receptor 2)

TJP1 TJP2 TJP3

PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions. Clostridium perfringens enterotoxin (CPE) induces cytolysis very rapidly through binding to its receptors CLDN3 and CLDN4

ONC: Overexpressed in ovarian [1], endometrial [2] and breast [3] carcinomas. Enhances invasion and is associated with increased matrix metalloproteinase-2 (MMP-2) activity [4]

[1] Rangel LB, Clin Cancer Res 2003, 9:2567-75. [2] Konecny GE, Gynecol Oncol 2008, 109:263-9. [3] Kominsky SL, Am J Pathol 2004, 164:1627-33. [4] Agarwal R, Cancer Res 2005, 65:7378-85

Claudin 4 CLDN4, CPER1 (Clostridium perfringens enterotoxin receptor 1)

Claudins TJP1 TJP2 TJP3

PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions. Clostridium perfringens enterotoxin (CPE) induces cytolysis very rapidly through binding to its receptors CLDN3 and CLDN4

ONC: Overexpressed in different carcinoma types (e.g. prostatic [1], ovarian [2], endometrial [3]). Plus, claudin-4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase-2 activity. However, decreased claudin-4 expression at the invasive front correlates colorectal cancer

[1] Landers KA, Br J Cancer 2008, 99:491-501. [2] Litkouhi B, Neoplasia 2007, 9:304-14. [3] Santin AD, Cancer 2007, 109:1312-22. [4] Agarwal R, Cancer Res 2005, 65:7378-85. [5] Ueda J, Pathobiology 2007, 74:32-41

MMMP Biomap #87

invasion and metastasis [5]

Claudin 5 CLDN5, AWAL, TMVCF (transmembrane protein deleted in velo-cardio-facial syndrome)

TJP1 TJP2 TJP3


ONC: Claudins 1, 2, 3, 4, 5 and 7 are expressed in different carcinomas (though with tumor type-specific differences). In contrast to epithelial tumors, lymphomas do not express claudins and most soft tissue tumors and nevocytic lesions are negative or show weaker, mainly cytoplasmic positivity for some claudins [1]

[1] Soini Y, Histopathology 2005, 46:551-60

Claudin 6 CLDN6 TJP1 TJP2 TJP3


ONC: Epigenetic silencing of claudin-6 promotes anchorage-independent growth of breast carcinoma cells [1]

[1] Osanai M, Cancer Sci 2007, 98:1557-62

Claudin 7 CLDN7, CEPTRL2 TJP1 TJP2 TJP3


ONC: Conflicting data. Downregulated in breast cancer, where its loss correlates with high grade tumors [6]. Hypermethylation-modulated downregulation of claudin-7 expression promotes the progression of colorectal carcinoma [1]. TCF-4 maintains low levels of claudin-7 at the bottom of colonic crypts, acting via SOX-9: this negative regulation is defective in colorectal cancer, possibly due to decreased SOX-9 activity, and the resulting claudin-7 overexpression promotes a loss of tumor cell polarization and contributes to tumorigenesis [2]. Plus, complex of EpCAM, claudin-7, CD44 variant isoforms, and tetraspanins promotes colorectal cancer progression [3]. However, reduced expression of the claudin-7 gene might lead to venous invasion and liver metastasis in colorectal cancer [4]. Plus, downregulation of claudin-7 leads to loss of E-cadherin expression and the increased

[1] Nakayama F, Pathobiology 2008, 75:177-85. [2] Darido C, Cancer Res 2008, 68:4258-68. [3] Kuhn S, Mol Cancer Res 2007, 5:553-67. [4] Oshima T, Oncol Rep 2008, 19:953-9. [5] Lioni M, Am J Pathol 2007, 170:709-21. [6] Kominsky SL, Oncogene 2003, 22:2021-33

MMMP Biomap #87

invasion of esophageal squamous cell carcinoma cells [5]

Claudin 8 CLDN8 TJP1 TJP2 TJP3


ONC: Downregulated in colorectal cancer at mRNA level but not protein level [1]

[1] Gröne J, Int J Colorectal Dis 2007, 22:651-9

Claudin 9 CLDN9 ? PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions [1]

ONC: -

[1] http://www.uniprot.org/uniprot/O95484

Claudin 10 CLDN10, OSP-L, CPETRL3 ? PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions [1]

ONC: Hepatocellular carcinoma (HCC) invasion is inhibited by suppression of claudin-10 [2] and claudin-10 expression is associated with recurrence of primary HCC [3]

[1] http://www.uniprot.org/uniprot/P78369. [2] Ip YC, Mol Cancer Ther 2007, 6:2858-67. [3] Cheung ST, Clin Cancer Res 2005, 11(2 Pt 1):551-6

Claudin 11 CLDN11, OTM (oligodendrocyte transmembrane protein)

Tetraspanin-3 PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions [1]

ONC: -


Claudin 12 CLDN12 ? PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions [1]

ONC: Upregulated in colorectal cancer at mRNA level but not protein level [1].

[1] Gröne J, Int J Colorectal Dis 2007, 22:651-9

Claudin 14 CLDN14 ? PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions. Defects in CLDN14 are the cause of non-syndromic sensorineural deafness autosomal recessive type 29 (DFNB29) [1]

ONC: -


Claudin 15 CLDN15 ? PHY: Calcium-independent cell-adhesion activity through the formation of tight junctions


MMMP Biomap #87

[1]

ONC: -

Claudin 16 CLDN16, paracellin-1 ? PHY: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Kidney-specific expression. Involved in paracellular magnesium reabsorption. Defects in CLDN16 are the cause of hypomagnesemia type 3 (HOMG3) [1]

ONC: Claudin-16 reduces the aggressive behavior of human breast cancer cells [2]. Claudin-16 and claudin-1 are upregulated in classic papillary thyroid carcinoma (PTC) but not in aggressive/poorly differentiated PTC [3]

[1] http://www.uniprot.org/uniprot/Q9Y5I7. [2] Martin TA, J Cell Biochem 2008, 105:41-52. [3] Fluge Ø, Thyroid 2006, 16:161-75

Claudin 17 CLDN17 ? PHY: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity [1]

ONC: -


Claudin 18 CLDN18, SFTPJ (surfactant associated protein J)

? PHY: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity

ONC: Immunohistochemical staining for claudin-18 is useful in the diagnosis of gastrointestinal signet ring cell carcinoma [1]. Overexpressed in pancreatic cancer [2]. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development [3]

[1] Sentani K, Am J Surg Pathol 2008, 32:1182-9. [2] Karanjawala ZE, Am J Surg Pathol 2008, 32:188-96. [3] Sahin U, Clin Cancer Res 2008, 14:7624-34

Claudin 19 CLDN19 ? PHY: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Defects in CLDN19 are the cause of hypomagnesemia renal with ocular involvement (HOMGO) [1]

[1] http://www.uniprot.org/uniprot/Q8N6F1

MMMP Biomap #87

ONC: -


ONC: -



ONC: -

[1] http://www.uniprot.org/uniprot/Q8N7P3

Claudin 23 CLDN23 ? PHY: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity. Expressed in germinal center B-cells, placenta, stomach [1]

ONC: Frequently downregulated in intestinal-type gastric cancer [2]

[1] http://www.uniprot.org/uniprot/Q96B33. [2] Katoh M, Int J Mol Med 2003, 11:683-9

DCHS1 Dachsous protein homolog 1, PCDH16, CDH19, fibroblast cadherin 1

? PHY: Calcium-dependent cell-adhesion protein belonging to the cadherin superfamily. Expressed in fibroblasts [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q96JQ0

DCHS2 Dachsous protein homolog 2, PCDH23, CDH27

? PHY: Calcium-dependent cell-adhesion protein belonging to the cadherin superfamily. Expressed in cerebral cortex and testis [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q6V1P9

DSC1 Desmocollin 1, CDHF1 Desmoglein PHY: Component of intercellular desmosome junctions, which connect adjacent cells and are linked to the cytoskeleton's intermediate filaments (e.g. cytokeratins, desmin, vimentin, nestin). Strongly expressed in epidermis, less in lymph node and tongue. Calcium may be bound by the cadherin-like repeats. May contribute to epidermal cell stratification [1]

[1] http://www.uniprot.org/uniprot/Q08554. [2] Khan K, Br J Cancer 2006, 95:1367-70

MMMP Biomap #87

ONC: Desmocollins (desmosomal cadherin family of cell-cell adhesion molecules) exhibit tissue-specific patterns of expression (e.g. only DSC2 is expressed in normal colonic epithelium). In colorectal carcinoma cells desmocollin switching leads to downregulation of DSC2 and de novo expression of DSC1 and DSC3 [2]

DSC2 Desmocollin 2, CDHF2 Desmoglein PHY: Component of intercellular desmosome junctions, which connect adjacent cells and are linked to the cytoskeleton's intermediate filaments (e.g. cytokeratins, desmin, vimentin, nestin). Expressed in epithelia, myocardium and lymph nodes. Calcium may be bound by the cadherin-like repeats. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms. Defects in DSC2 are the cause of familial arrhythmogenic right ventricular dysplasia 11 (ARVD11) [1]

ONC: The desmocollins (desmosomal cadherin family of cell-cell adhesion molecules) exhibit tissue-specific patterns of expression (e.g. only DSC2 is expressed in normal colonic epithelium). In colorectal cancer desmocollin switching leads to downregulation of DSC2 and de novo expression of DSC1 and DSC3 [2]


DSC3 Desmocollin 3, CDHF3 Desmoglein PHY: Component of intercellular desmosome junctions, which connect adjacent cells and


MMMP Biomap #87

are linked to the cytoskeleton's intermediate filaments (e.g. cytokeratins, desmin, vimentin, nestin). Expressed in epidermis, buccal mucosa, esophagus and cervix. Calcium may be bound by the cadherin-like repeats. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms [1]

ONC: The desmocollins (desmosomal cadherin family of cell-cell adhesion molecules) exhibit tissue-specific patterns of expression (e.g. only DSC2 is expressed in normal colonic epithelium). In colorectal cancer desmocollin switching leads to downregulation of DSC2 and de novo expression of DSC1 and DSC3 [2]

DSCAM Down syndrome cell adhesion molecule, CHD2-42, CHD2-52

DSCAM PHY: Mediates cation-independent homophilic binding activity. Could be involved in nervous system development

ONC: -

[1] Schmucker D, Nat Rev Neurosci 2007, 8:915-20

DSCAML1 DSCAM like 1 DSCAML1 PHY: Mediates cation-independent homophilic binding activity. Could be involved in nervous system development

ONC: In acute leukemia cells, one of the several different translocation partner genes of mixed lineage leukemia (MLL) gene [1]

[1] Kowarz E, Leukemia 2007, 21:1232-8

DSG1 Desmoglein 1, CDHF4 Desmocollin PHY: Component of intercellular desmosome junctions, which connect adjacent cells and are linked to the cytoskeleton's intermediate filaments (e.g. cytokeratins, desmin, vimentin, nestin). Expressed in epidermis, tongue, tonsil and esophagus. Calcium may be bound by the cadherin-like repeats. Defects in DSG1 are the cause of palmoplantar keratoderma striate

[1] http://www.uniprot.org/uniprot/Q02413. [2] Romani VC, BMC Cancer 2008, 8:373. [3] Wong MP, Pathology 2008, 40:611-6. [4] Fukuoka J, Hum Pathol 2007, 38:276-83. [5] Schmitt CJ, J Invest Dermatol 2007, 127:2191-206. [6] Li G, Oncogene 2001, 20:8125-35

MMMP Biomap #87

type 1 (SPPK1) [1]

ONC: Loss in desmogleins (desmosomal proteins of the cadherin family) is described in different tumor types, and is believed to promote cancer invasiveness [2-4]. In melanoma, desmogleins can be expressed but do not form desmosomes [5] and are downregulated by c-MET during progression [6]

DSG2 Desmoglein 2, CDHF5 Desmocollin PHY: Component of intercellular desmosome junctions, which connect adjacent cells and are linked to the cytoskeleton's intermediate filaments (e.g. cytokeratins, desmin, vimentin, nestin). Expressed in most tissues tested and carcinomas. Calcium may be bound by the cadherin-like repeats. Defects in DSG2 are the cause of familial arrhythmogenic right ventricular dysplasia 10 (ARVD10) [1]

ONC: Loss in desmogleins (desmosomal proteins of the cadherin family) is described in different tumor types, and is believed to promote cancer invasiveness [2-4]. In melanoma, desmogleins can be expressed but do not form desmosomes [5] and are downregulated by c-MET during progression [6]

[1] http://www.uniprot.org/uniprot/Q14126. [2] Romani VC, BMC Cancer 2008, 8:373. [3] Wong MP, Pathology 2008, 40:611-6. [4] Fukuoka J, Hum Pathol 2007, 38:276-83. [5] Schmitt CJ, J Invest Dermatol 2007, Sep;127(9):2191-206. [6] Li G, Oncogene. 2001 Dec 6;20(56):8125-35

DSG3 Desmoglein 3, CDHF6 Desmocollin PHY: Component of intercellular desmosome junctions, which connect adjacent cells and are linked to the cytoskeleton's intermediate filaments (e.g. cytokeratins, desmin, vimentin, nestin). Expressed in epidermis, tongue, tonsil, esophagus and carcinomas. Calcium may be bound by the cadherin-like repeats. Pemphigus vulgaris is a potentially lethal skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion likely caused by autoantibodies against desmoglein-3 [1]

ONC: Loss in desmogleins (desmosomal

[1] http://www.uniprot.org/uniprot/P32926. [2] Romani VC, BMC Cancer 2008, 8:373. [3] Wong MP, Pathology 2008, 40:611-6. [4] Fukuoka J, Hum Pathol 2007, 38:276-83. [5] Schmitt CJ, J Invest Dermatol 2007, 127:2191-206. [6] Li G, Oncogene 2001, 20:8125-35

MMMP Biomap #87

proteins of the cadherin family) is described in different tumor types, and is believed to promote cancer invasiveness [2-4]. In melanoma, desmogleins can be expressed but do not form desmosomes [5] and are downregulated by c-MET during progression [6]

DSG4 Desmoglein 4, CDHF13 Desmocollin PHY: DSG4 (desmosomal protein of the cadherin family) is highly expressed in skin, testis and prostate; less in salivary gland. In scalp follicles, present in the inner rooth sheath (IRS) and all layers of the matrix and precortex. Calcium may be bound by the cadherin-like repeats. Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Coordinates the transition from proliferation to differentiation in hair follicle keratinocytes. Defects in DSG4 are the cause of localized autosomal hypotrichosis (LAH). DSG4 is one of the target molecules recognized by autoantibodies in patients with pemphigus vulgaris [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q86SJ6

Endomucin MUC14, EMCN ? PHY: Endothelial sialomucin that interferes with the assembly of focal adhesion complexes and inhibits interaction between cells and the extracellular matrix. Endothelial marker. marks hematopoietic stem cells throughout development [1]

ONC: -

[1] Matsubara A, J Exp Med 2005, 202:1483-92

EPCAM Epithelial cell adhesion molecule, Ep-CAM, MIC18, Ly74, TROP1, GA733-2, EGP34, EGP40, EGP-2, KSA, CD326, Ep-CAM, HEA125, KS1/4, MK-1, MH99, MOC31, 323/A3, 17-1A, TACST-1 (tumor-associated calcium signal transducer 1), CO-17A, ESA

EPCAM PHY: This protein is expressed in almost all epithelial cell membranes but not on mesodermal or neural cell membranes. Mediates calcium-independent homotypic cell-cell adhesions [6]. Upon (over-) expression of Ep-CAM, cadherin adhesions dissociate, which leads to accumulation of soluble E-cadherin/ beta-catenin complexes: this

[1] Schmidt M, Clin Cancer Res 2008, 14:5849-55. [2] Gosens MJ, Mod Pathol 2007, 20:221-32. [3] Tai KY, Oncogene 2007, 26:3989-97. [4] Fong D, J Clin Pathol 2008, 61:31-5. [6] Winter MJ, Am J Pathol 2003, 163:2139-48. [7] Baeuerle PA, Br J Cancer 2007, 96:417-23. [8] Le Naour F, Front Biosci 2008, 13:5847-65

MMMP Biomap #87

suggests that during cell division, the strong E-cadherin-mediated cellular adhesion is abrogated, while the weaker intercellular adhesion mediated by Ep-CAM still holds the cell in place; after the proliferative phase, Ep-CAM expression declines and higher levels of E-cadherin mediate intercellular adhesions [6]

ONC: Ep-CAM overexpression is associated with poor survival in breast cancer [1]. However, loss of membranous Ep-CAM is associated with nuclear beta-catenin localization and contributes to reduced cell-cell adhesions, increased migratory potential and tumor budding in colon cancer [2]. Plus, forced expression of Ep-CAM decreases cancer invasiveness while silencing Ep-CAM expression enhances cancer invasiveness [3]. Is strongly expressed in a variety of epithelial cancers and represents a promising target for active (vaccination) and passive (e.g. anti-EPCAM antibody edrecolomab) anticancer immunotherapy [4]. Used as a pan-carcinoma marker [6] (e.g. for sorting/ detection of circulating tumor cells). Identified as one of the first tumor associated antigens, its role in cancer biology is being elucidated [7,8]

ESAM Endothelial specific adhesion molecule, W117m

ESAM PHY: Likely mediates homophilic binding activity. Involved in tight junction formation. Supports neutrophil extravasation [1]

ONC: Associated with tumor spread to lymphatics [2] also in melanoma [3]

[1] Wegmann F, J Exp Med 2006, 203:1671-7. [2] Clasper S, Cancer Res 2008, 68:7293-303. [3] Ishida T, J Biol Chem 2003, 278:34598-604

FAT1 Fat tumor suppressor homolog 1, CDHF7, Fat cadherin 1, protocadherin Fat 1

? PHY: Expressed in many epithelial and some endothelial and smooth muscle cells. Involved in cell-cell contacts (homophilic interaction ?) and lamellipodial dynamics (by binding to Ena/VASP proteins) [1]

ONC: Tumor suppressor gene in Drosophila, may act as a receptor of the Hippo signaling pathway [2] (a tumor suppressor pathway in

[1] Tanoue T, J Cell Sci 2005, 118 (Pt 11):2347-53. [2] Willecke M, Curr Biol 2006, 16:2090-100. [3] Zeng Q, Cancer Cell 2008, 13:188-92. [4] Kwaepila N, Pathology 2006, 38:125-31

MMMP Biomap #87

humans [3]). However, its over-expression and diffuse expression in both in situ and invasive carcinoma strongly suggests a role in breast carcinogenesis [4]


? PHY: FAT2 mRNA is expressed in infant brain and cerebellum [1]

ONC: FAT2 mRNA is expressed in gastric cancer, pancreatic cancer, ovarian cancer, esophageal cancer, skin squamous cell carcinoma, head and neck cancer [1]. Knockdown of Fat2 by siRNA inhibits the migration of human squamous carcinoma cells

[1] Katoh Y, Int J Mol Med 2006, 18:523-8. [2] Matsui S, J Dermatol Sci 2008, 51:207-10


? PHY: Expressed in embryonic stem cells, primitive neuroectoderm, fetal brain, infant brain, adult neural tissues and prostate [1]. May play a role in the interactions between neurites derived from specific subsets of neurons during development [2]

ONC: -

[1] Katoh Y, Int J Mol Med 2006, 18:523-8. [2] http://www.uniprot.org/uniprot/Q8TDW7


? PHY: Widely expressed. Expressed in fetal and infant brain [1]. Fat4 regulates vertebrate planar cell polarity [2]

ONC: Expressed in brain tumor and colorectal cancer [1]

[1] Katoh Y, Int J Mol Med 2006, 18:523-8. [2] Saburi S, Nat Genet 2008, 40:1010-5

GJA1 Gap junction alpha 1 protein, Connexin-43, CX43 (43 kDa)

Connexins PHY: Expressed in the heart and fetal cochlea. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear

[1] http://www.uniprot.org/uniprot/P17302. [2] Li Z, Clin Exp Metastasis 2008, 25:893-901. [3] Elzarrad MK, BMC Med 2008, 6:20. [4] Geng S, Cell Biol Int 2007, 31:1420-7. [5] Zhang D, Cancer Lett 2007, 252:208-15. [6] Haass NK, J

MMMP Biomap #87

CONNEXINS

Connexons consist of six subunits, connexins. A connexon may be homomeric (i.e. composed of six identical connexin subunits) or heteromeric (i.e. including more than one species of connexins). Connexons associate end to end to form a double-membrane gap junction channel. The channel may be homotypic (identical connexons) or heterotypic (two different connexons). Gap junctions mediate diffusion of low molecular weight from one cell to a neighboring cell and are involved in many physiological processes (e.g. electrical signal transmission) as well as in the genesis of diseases (e.g. cancer progression). REFERENCES: [1] Evans WH, Biochem J 2006, 397:1-14. [2] Cronier L, Antioxid Redox Signal 2009, 11:323-38

endolymph. Defects in GJA1 are the cause of oculodentodigital dysplasia (ODDD) and hypoplastic left heart syndrome (HLHS) [1]

ONC: Conflicting data on the role of this connexin in cancer progression [2-5], although the majority of the reports are in favor of a tumor suppressive activity (including in melanoma [6,7]). Is upregulated by cancer preventing agents such as carotenoids and retinoids [8]. Its expression on dendritic cells (DC) appears important for melanoma antigen cross-presentation [9]

Mol Histol 2004, 35:309-18. [7] Daniel-Wójcik A, Int J Oncol 2008, 33:309-15. [8] Bertram JS, Biochim Biophys Acta 2005, 1740:170-8. [9] Mendoza-Naranjo A, J Immunol 2007, 178:6949-57


Connexins PHY: Is a component of lens fiber gap junctions. Defects in GJA3 are the cause of zonular pulverulent cataract type 3 (CZP3) [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9Y6H8


Connexins PHY: Expressed in multiple organs and tissues, including heart, uterus, ovary, and blood vessel endothelium [1]

ONC: -



Connexins PHY: Defects in GJA5 are a cause of idiopathic atrial fibrillation [1]

ONC: -



Connexins PHY: Expressed in eye lens. Defects in GJA8 are a cause of autosomal dominant congenital cataract [1]

ONC: -



Connexins PHY: Highly abundant in skeletal muscle. Also detected in testis [1]

ONC: -



Connexins PHY: Expressed in skeletal muscle and heart. Involved in tracer coupling between horizontal

[1] http://www.uniprot.org/uniprot/Q969M2

MMMP Biomap #87

cells of the retina [1]

ONC: -

GJB1 Gap junction beta 1 protein, Connexin-32, CX32 (32 kDa)

Connexins PHY: Defects in GJB1 are the cause of Charcot-Marie-Tooth disease X-linked type 1 (CMTX1), a form of Charcot-Marie-Tooth disease, the most common inherited disorder of the peripheral nervous system [1]

ONC: Demethylating agent 5-aza-CdR suppresses the growth of human renal cell carcinoma (RCC) in a xenograft model by restoring Cx32 expression [2]. Connexin 32 potentiates vinblastine-induced cytotoxicity in RCC cells [3]

[1] http://www.uniprot.org/uniprot/P08034. [2] Hagiwara H, Br J Pharmacol 2008, 153:1373-81. [3] Sato H, Mol Carcinog 2007, 46:215-24


Connexins PHY: Defects in GJB2 are a cause of non-syndromic sensorineural deafness

ONC: Increased expression of GJB2 is associated with tumor progression in different models [1,2], including melanoma [3,4]. Opposite findings have also been reported [5]

[1] Ezumi K, Clin Cancer Res 2008, 14:677-84. [2] Naoi Y, Cancer Lett 2008, 262:248-56. [3] Nojima H, Curr Drug Saf 2007, 2:204-11. [4] Saito-Katsuragi M, Cancer 2007, 110:1162-72. [5] McLachlan E, Cancer Res 2006, 66:9886-94


Connexins PHY: Defects in GJB3 are a cause of erythrokeratodermia variabilis (EKV) and a cause of non-syndromic sensorineural deafness [1]

ONC: -


GJB4 Gap junction beta 4 protein, Connexin-30.3, CX30.3 (30.3 kDa)

Connexins PHY: Defects in GJB4 are a cause of erythrokeratodermia variabilis (EKV) [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9NTQ9

GJB5 Gap junction beta 5 protein, Connexin-31.1, CX31.1 (31.1 kDa)

Connexins PHY: ?

ONC: -

-


Connexins PHY: Defects in GJB6 are the cause of ectodermal dysplasia type 2 (ED2)

ONC: Decreased expression of connexin 30 (and aberrant expression of connexin-26) in

[1] Ozawa H, Anticancer Res 2007, 27(4B):2189-95

MMMP Biomap #87

human head and neck cancer [1]


Connexins PHY: ?

ONC: -

-

GJC1 Gap junction gamma 1 protein, Connexin-45, CX45 (45 kDa)

Connexins PHY: ?

ONC: -

-

GJC2 Gap junction gamma 2 protein, Connexin-47, CX47 (47 kDa)

Connexins PHY: May play a role in myelination in central and peripheral nervous systems. Defects in GJC2 are the cause of Pelizaeus-Merzbacher-like disease autosomal recessive type 1 (PMLD1), an autosomal recessive hypomyelinating leukodystrophy [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q5T442

GJC3 Gap junction gamma 3 protein, Connexin-30.2, CX30.2 (30.2 kDa)

Connexins PHY: Mainly expressed in brain, spinal cord, and sciatic nerve. Also expressed in skeletal muscle, liver and heart [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q8NFK1

GJD2 Gap junction delta 2 protein, Connexin-36, CX36 (36 kDa)

Connexins PHY: Highly expressed in neurons [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9UKL4

GJD3 Gap junction delta 3 protein, Connexin-31.9, CX31.9 (31.9 kDa)

Connexins PHY: Widely expressed [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q8N144

GJD4 Gap junction delta 4 protein, Connexin-40.1, CX40.1 (40.1 kDa)

Connexins PHY: Widely expressed [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q96KN9

GJE1 Gap junction epsilon 1 protein, Connexin-23, CX23 (23 kDa)

Connexins PHY: ?

ONC: -

-

HEPACAM Hepatocyte cell adhesion molecule, HEPN1, FLJ25530

Fibronectin (?) PHY: Increases cell spreading on the matrices fibronectin and matrigel, delays cell detachment, and enhances wound healing [1]

ONC: Downregulated in HCC [2]. Induces growth arrest via a p53/p21-dependent

[1] Moh MC, J Biol Chem 2005, 280:27366-74. [2] Moh MC, J Hepatol 2003, 39:580-6. [3] Moh MC, Carcinogenesis 2008, 29:2298-305

MMMP Biomap #87

pathway in human breast cancer cells [3]

ICAM1 Intercellular adhesion molecule 1, CD54 ITG alpha L-beta2 PHY: Mainly expressed on endothelial cells. Involved in leukocyte trans-endothelial migration. Interacts with MUC1 (expressed by epithelial cells). Is a Rhinovirus receptor

ONC: Promotes the metastatic process of different cancer types [1,2] including melanoma [3,4]. Low expression of ICAM1 in melanoma specimens might underlie insufficient recruitment of cytotoxic T lymphocytes and thus limit the effectiveness of immunotherapy regimens [5]

[1] Rahn JJ, Clin Exp Metastasis 2005, 22:475-83. [2] Takahashi M, Clin Exp Metastasis 2008, 25:517-29. [3] Wang S, Int J Cancer 2006, 118:932-41. [4] Hamai A, Cancer Res 2008, 68:9854-64. [5] Weishaupt C, Clin Cancer Res 2007, 13:2549-56

ICAM2 Intercellular adhesion molecule 2, CD102 ITG alpha L-beta2 PHY: Lymphocyte recirculation (by blocking LFA-1-dependent cell adhesion). Adhesive interactions important for antigen-specific immune response

ONC: Expressed on cancer cells, it enhances NK cell adhesion to and activation against them [1]. When expressed on endothelial cells inhibits dendritic cell based anticancer immune response [2]

[1] Tanaka H, Clin Cancer Res 2004, 10:4885-92. [2] Malero I, Cancer Res 2002, 62:3167-74

ICAM3 Intercellular adhesion molecule 3, CD50, ICAM-R, CDW50

ITG alpha L-beta2 ITG alpha D-beta2

PHY: Involved in leukocyte function

ONC: Induces cancer cell proliferation through the PI3K/Akt pathway [1]. Associated with cancer resistance to radiotherapy [2]

[1] Kim YG, Cancer Lett 2006, 239:103-10. [2] Chung YM, Int J Cancer 2005, 117:194-201

ICAM4 Intercellular adhesion molecule 4, CD242 ITG alpha L-beta2 ITG alpha4-beta1

PHY: Determines the Landsteiner-Wiener blood group [1]

ONC: -

[1] Toivanen A, Biochim Biophys Acta 2008, 1780:456-66

ICAM5 Intercellular adhesion molecule 5, Telencephalin

ITG alpha L-beta2 ICAM5

PHY: Expressed by neurons of the telencephalon; regulation of immunological activity in the brain [1,2]

ONC: -

[1] Gahmberg CG, Immunol Lett 2008, 117:131-5. [2] Tian L, Blood 2008, 111:3615-25

MMMP Biomap #87

ITGA1 Integrin alpha 1, CD49a Collagen Laminin

INTEGRINS (ITGs) Integrins are alpha-beta heterodimeric receptors that connect the extracellular environment with intracellular signaling events. Integrins are important for normal development and function, but are also involved in the pathogenesis of diseases including cancer, autoimmunity and heart disease. Besides cell adhesion, integrins mediate cell signaling via activation of molecular cascades such as those initiated by ILK (integrin linked kinase), FAK (focal adhesion kinase) and SFK (SRC family kinases) multifunctional intracellular effectors of cell-matrix interactions that regulates many cellular processes including growth, proliferation, survival, differentiation, migration, invasion and angiogenesis. REFERENCES: [1] McDonald PC, J Cell Sci. 2008 Oct 1;121(Pt 19):3121-32. [2] Guo W, Nat Rev Mol Cell Biol 2004, 5:816-26. [3] McCall-Culbreath KD, Curr Drug Targets. 2008 Feb;9(2):139-49

PHY: Heterodimer with integrin beta 1 (VLA1, CD49a/CD29)

ONC: Modulates adhesion of hepatocellular carcinoma (HCC) cells to extracellular matrix (ECM) protein laminin alpha 5 [1] (laminins are a diverse group of alpha/beta/gamma

heterotrimers formed from five alpha, three beta and three gamma chains). Obtustatin, a snake venom KTS-disintegrin, is a specific inhibitor of this integrin and completely blocks cancer growth of MV3 human melanoma in nude mice [2]. K-RAS and integrin alpha1-beta1 cooperate to drive the growth of non-small cell lung cancer (NSCLC) in vivo [3]

[1] Kikkawa Y, Exp Cell Res 2008, 314:2579-90. [2] Brown MC, Int J Cancer 2008, 123:2195-203. [3] Macias-Perez I, Cancer Res 2008, 68:6127-35

ITGA2 Integrin alpha 2, CD49b Collagen Laminin Fibronectin E-cadherin

INTEGRIN HETERODIMERS For a synoptic view of all integrin heterodimers, please visit the dedicated MMMP Biomap # 85 at the following address: http://www.mmmp.org/MMMP/public/biomap/viewBiomap.mmmp?id=86

PHY: Heterodimer with integrin beta 1 (VLA2, CD49b/CD29). It is responsible for adhesion of platelets and other cells to extracellular matrix (ECM)

ONC: Polymorphisms of this gene are associated with the risk of developing breast carcinoma [1]. VLA2 plays an important role in angiogenesis via regulation of VEGFR1 expression: when challenged with B16F10 melanoma cells, mice lacking VLA2 expression exhibit increased tumor angiogenesis associated with upregulated VEGFR1 expression [2]. High mRNA expression of integrin alpha2 is associated with poorer overall survival of melanoma patients [3]

[1] Langsenlehner U, Breast Cancer Res Treat 2006, 97:67-72. [2] Zhang Z, Blood 2008, 111:1980-8. [3] Vuoristo M, Melanoma Res 2007, 17:215-23

ITGA2B Integrin alpha 2b, platelet glycoprotein IIb Fibrinogen PHY: Heterodimer with integrin beta 3 [1] http://www.uniprot.org/uniprot/P08514

MMMP Biomap #87

(GP2B), CD41 Fibronectin Vitronectin Thrombospondin Von Willebrand factor

(GPIIb/IIIa, CD41/CD61). Involved in platelet adhesion and aggregation (defects in ITGA2B cause Glanzmann thrombasthenia). Recognizes the sequence RGD in a wide array of ligands. Isoform-1 and isoform-2 are mainly expressed by platelets and megakaryocytes. Utilized as a platelet marker [1]

ONC: Isoform-3 is expressed by leukemia, prostate adenocarcinoma and melanoma cells but not by platelets or normal prostate or breast epithelial cells [1]

ITGA3 Integrin alpha 3, CD49c, VCA-2, GAPB3 (galactoprotein B3), MSK18

Fibronectin Collagen Laminin Epiligrin Thrombospondin CSPG4

PHY: Heterodimer with integrin beta 1 (VLA-3, CD49c/CD29). May mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration [1]. Isoforms (3A and 3B) are differentially expressed in tissues [3]

ONC: The invasive and metastatic potential of hepatocellular carcinoma (HCC) are positively correlated with the expression level of integrin alpha3-beta1, whose expression is enhanced by transforming growth factor (TGF)beta-1 [2]

[1] Fukushi J, Mol Biol Cell 2004, 15:3580-3590. [2] Katabami K, Clin Exp Metastasis 2005, 22:539-48. [3] http://www.uniprot.org/uniprot/P26006

ITGA4 Integrin alpha 4, CD49d Fibronectin VCAM1 MadCAM1

PHY: Heterodimer with integrin beta 1 (VLA-4, CD49d/CD29) and integrin beta 7. On activated endothelial cells, integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytotoxic T-cell interactions with target cells

ONC: Gambogic acid downregulates ITGA4 expression and inhibits the adhesion and migration of B16-F10 melanoma cells in vitro and in vivo [1]. Integrin VLA-4 enhances sialyl-Lewisx/a-negative melanoma adhesion to and extravasation through the endothelium [2]. On the other hand, ITGA4 hypermethylation is associated with esophageal cancer recurrence [3]; plus, STAT6 signaling suppresses VLA-4 expression by CD8+ T cells and limits their

[1] Zhao J, Eur J Pharmacol 2008, 589:127-31. [2] Liang S, Am J Physiol Cell Physiol 2008, 295:C701-7. [3] Lee EJ, Int J Cancer 2008, 123:2073-9. [4] Sasaki K, J Immunol 2008, 181:104-8

MMMP Biomap #87

ability to infiltrate tumor lesions in vivo [4]

ITGA5 Integrin alpha 5, CD49e, FNRA (fibronectin receptor subunit alpha)

Fibronectin Fibrinogen

PHY: Heterodimer with integrin beta 1 (VLA-5, CD49e/CD29) [1]. It recognizes the sequence RGD in its ligands [2]. Promotes angiogenesis [5]

ONC: ADAM15 suppresses cell motility by driving VLA-5 expression (via ERK inactivation) and reduces lung metastasis in a murine melanoma model [3]. VLA-4 promotes melanoma cell migration by inhibiting VLA-5 induced focal adhesions [7]. On the other side, VLA-5 blocking antibodies have anticancer activity in xenograft models [4] and ADAM15 recombinant disintegrin domain (RDD, which contains an RGD sequence and binds to both VLA-5 and integrin alphaV-beta3) has anticancer effect in an in vivo murine melanoma model [6]

[1] Huveneers S, Int J Radiat Biol 2007, 83:743-51. [2] http://www.uniprot.org/uniprot/P08648. [3] Chen Q, Int J Biochem Cell Biol 2008, 40:2164-73. [4] Bhaskar V, J Transl Med 2007, 5:61. [5] Kim S, Am J Pathol 2000, 156:1345-62. [6] Trochon-Joseph V, Cancer Res 2004, 64:2062-9. [7] Moyano JV, Mol Biol Cell 2003, 14:3699-715

ITGA6 Integrin alpha 6, CD49f Laminin PHY: Heterodimer with integrin beta 1 (VLA-6, CD49f/CD29) or integrin beta 4 (CD49f/CD104). Laminin receptor on platelets (VLA-6) and epithelial cells (CD49f/CD104) [1]. Defects in ITGA6 are a cause of epidermolysis bullosa with pyloric atresia (EBPA) [1]. Tetraspanin CD151 promotes cell migration by regulating trafficking of integrins alpha3-beta1, alpha5-beta1 and alpha6-beta1 [2]

ONC: An epitope on VLA-6 involved in migration but not adhesion is required for extravasation of murine melanoma B16F1

[1] http://www.uniprot.org/uniprot/P23229. [2] Liu L, J Biol Chem 2007, 282:31631-42. [3] Hangan D, Cancer Res 1997, 57:3812-7. [4] Colomiere M, Int J Biochem Cell Biol 2008, Epub ahead of print. [5] Huang Y, Biochem Biophys Res Commun 2008, 377:474-8. [6] Dutta U, Cancer Res 2008, 68:8779-87. [7] Tsuruta D, Curr Med Chem 2008, 15:1968-75

MMMP Biomap #87

cells in liver [3]. Neutralizing antibodies against alpha6 and beta1 subunits inhibit ovarian cancer cell migration [4]. Midkine promotes tetraspanin-VLA-6 interaction and induces FAK-STAT1alpha pathway contributing to migration/ invasiveness of human head&neck squamous cell carcinoma cells [5]. Expression of integrin alpha6-beta4 is associated with poor patient prognosis and reduced survival in a variety of human cancers and a key tyrosine (Y1494) in the beta4 integrin regulates multiple signaling pathways important for tumor development and progression [6]. Laminin-332-integrin (VLA-3 and alpha6-beta4) interaction is being investigated as a target for cancer therapy [7]

ITGA7 Integrin alpha 7, CD49g Laminin PHY: Heterodimer with integrin beta 1 (CD49g/CD29). Originally identified in melanoma, is the primary laminin receptor on skeletal myoblasts and adult myofibers. Defects in ITGA7 are associated with a form of congenital myopathy [1]

ONC: Expression of the alpha7-beta1 laminin receptor suppresses melanoma growth and metastatic potential [2]

[1] http://www.uniprot.org/uniprot/Q13683. [2] Ziober BL, Cell Growth Differ 1999, 10:479-90

ITGA8 Integrin alpha 8, CD49h Tenascin-C Fibronectin-1 Vitronectin Osteopontin

PHY: Heterodimer with integrin beta 1 (CD49h/CD29). Functions in the genesis of kidney and probably of other organs by regulating the recruitment of mesenchymal cells into epithelial structures; it recognizes the sequence RGD in a wide array of ligands [1]

ONC: -


ITGA9 Integrin alpha 9, Integrin alpha RLC VCAM1 Cytotactin Osteopontin Tenascin-C NGF [4]

PHY: Heterodimer with integrin beta 1. Expressed in airway epithelium, basal layer of squamous epithelium, smooth muscle, skeletal muscle and hepatocytes [1]. Three non-RGD-containing disintegrins (VLO5, EO5 and EC3) belong to the heterodimeric family of snake venom-derived proteins: they are potent inhibitors of certain leukocyte integrins such

[1] http://www.uniprot.org/uniprot/Q13797. [2] Bazan-Socha S, Biochemistry 2004, 43:1639-47. [3] Singh P, J Invest Dermatol 2009, 129:217-28. [4] Staniszewska I, J Cell Sci 2008, 121(Pt 4):504-13. [5] Fiorilli P, Lab Invest 2008, 88:1143-56

MMMP Biomap #87

as alpha4-beta1, alpha4-beta7, and alpha9-beta1. Loss of integrin alpha9-beta1 results in defects in proliferation, causing poor re-epithelialization during cutaneous wound healing [3]

ONC: Abundantly expressed in fetal lung and lung cancers [1]. Mediates adhesion of medulloblastoma cells to tenascin and activate pathways associated with survival and proliferation [5]

ITGA10 Integrin alpha 10 Collagen PHY: Heterodimer with integrin beta 1. Widely expressed with highest expression in muscle and heart [1]

ONC: Cell adhesion receptors, including the integrin-type collagen receptors (alpha1-beta1, alpha2-beta1, alpha10-beta1 and alpha11-beta1) participate in cancer progression and invasion. Quantitative RT-PCR indicated that all 4 receptors are abundantly expressed in sarcoma-derived cell lines, whereas most carcinoma-derived cells express alpha1-beta1 and alpha2-beta1 only [2]

[1] http://www.uniprot.org/uniprot/O75578. [2] Mirtti T, Int J Cancer 2006, 118:889-98

ITGA11 Integrin alpha 11 Collagen PHY: Heterodimer with integrin beta 1. Expressed in most tissues (low levels in peripheral blood lymphocytes) [1]

ONC: Cell adhesion receptors, including the integrin-type collagen receptors (alpha1-beta1, alpha2-beta1, alpha10-beta1 and alpha11-beta1) participate in cancer progression and invasion. Quantitative RT-PCR indicated that all 4 receptors are abundantly expressed in sarcoma-derived cell lines, whereas most carcinoma-derived cells express alpha1beta1 and alpha2beta1 only [2]

[1] http://www.uniprot.org/uniprot/Q9UKX5. [2] Mirtti T, Int J Cancer 2006, 118:889-98

ITGAD Integrin alpha D, Leukointegrin alpha D, ADB2, CD11d

ICAM3 VCAM1

PHY: Heterodimer with integrin beta 2. May play a role in the atherosclerotic process such as clearing lipoproteins from plaques and in phagocytosis of blood-borne pathogens,


MMMP Biomap #87

particulate matter, and senescent erythrocytes from the blood [1]

ONC: -

ITGAE Integrin alpha E, CD103, HML-1 (human mucosal lymphocyte antigen 1)

E-cadherin PHY: Heterodimer with integrin beta 7. Mediates adhesion of intra-epithelial T-lymphocytes to epithelial cell monolayers (Expressed on a subclass of T-lymphocytes known as intra-epithelial lymphocytes which are located between mucosal epithelial cells) [1]

ONC: Interaction of epithelial cell marker E-cadherin (often lost during tumor progression)with integrin alpha E/beta7 (expressed by tumor-infiltrating lymphocytes, TIL) plays a major role in effective tumor cell lysis [2]; this integrin can be upregulated upon TCR engagement and by TGFb1 treatment, resulting in strong potentiation of antitumor lytic function [2]

[1] http://www.uniprot.org/uniprot/P38570. [2] Le Floc'h A, J Exp Med 2007, 204:559-70

ITGAL Integrin alpha L, CD11a ICAM1 ICAM2 ICAM3 ICAM4

PHY: Heterodimer with integrin beta 2 (LFA-1, CD11a/CD18). Mainly expressed by leukocytes. Involved in a variety of immune phenomena including leukocyte-endothelial cell interaction, cytotoxic T-cell (CTL) mediated killing, and antibody dependent killing by granulocytes and monocytes [1]

ONC: LFA-1 is required for adequate immune response against cancer [2,3]

[1] http://www.uniprot.org/uniprot/P20701. [2] Smith A, Immunol Rev 2007, 218:135-46. [3] Jenkinson SR, J Immunol 2005, 174:3401-7

ITGAM Integrin alpha M, CD11b, MAC-1 C3b Fibrinogen ICAM1

PHY: Heterodimer with integrin beta 2 (CD11b/CD18). Mainly expressed in monocytes and granulocytes. Adhesion of monocytes, macrophages and granulocytes. Uptake of complement-coated particles (recognizes the RGD sequence in C3b) [1]

ONC: Expression of MAC-1 (CD11b) in acute myeloid leukemia (AML) is associated with an unfavorable prognosis [2]

[1] http://www.uniprot.org/uniprot/P11215. [2] Graf M, Am J Hematol 2006, 81:227-35

MMMP Biomap #87

ITGAV Integrin alpha V, CD51 Vitronectin Fibrinogen Fibronectin Thrombospondin Von Willebrand factor Osteopontin Collagen

PHY: Heterodimer with integrin beta 3 (CD51/CD61, VNR [vitronectin receptor]), integrin beta 5, integrin beta 6 and integrin beta 8. Recognizes the RGD sequence in its ligands.

ONC: CD51/CD61 plays a key role in angiogenesis and tumor metastasis in many tumor models, including melanoma [4]. It is expressed on activated endothelial cells as well as some tumor cells but is not present in resting endothelial cells and most normal organ systems, which makes it a suitable target for anti-angiogenic cancer therapy [1,2,3] by means of different molecules such as RGD-containing peptides and antibodies, some of them being under clinical investigation (e.g. cilengitide [5], vitaxin [6], etaracizumab [7]). Of note, blocking the adhesive function of integrin alphaVbeta3 with soluble RGD ligands (e.g. osteopontin, cilengitide) promotes VLA-5 recycling and marked increase in fibronectin-dependent migration of tumor cells into 3D matrices [8].

[1] Cai W, Anticancer Agents Med Chem 2006, 6:407-28. [2] Dayam R, J Med Chem 2006, 49:4526-34. [3] Boswell CA, Mol Pharm 2008, 5:527-39. [4] Li X, J Cell Sci 2001, 114 (Pt 14):2665-72. [5] Reardon DA, Expert Opin Investig Drugs 2008, 17:1225-35. [6] Gramoun A, J Cell Biochem 2007, 102:341-52. [7] Delbaldo C, Invest New Drugs 2008, 26:35-43. [8] Caswell PT, J Cell Biol 2008, 183:143-55.

ITGAX Integrin alpha X, CD11c, Leu M5 (leukocyte adhesion receptor p150)

Fibrinogen PHY: Heterodimer with integrin beta 2 (CD11c/CD18). Mediates cell-cell interaction during inflammatory responses; especially important in monocyte adhesion and chemotaxis [1]

ONC: -


ITGB1 Integrin beta 1, CD29, GPIIA See integrins ITGA1 to ITGA11 for details

PHY: Heterodimer with ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGA7, ITGA8, ITGA9, ITGA10, ITGA11. See these integrins for details

ONC: Signaling mediated by ITGB1 is believed to promote development and progression of cancer [1,2], including melanoma [3]. See integrins ITGA1 to ITGA11 for more details

[1] Barkan D, Cancer Res 2008, 68:6241-50. [2] Brockbank EC, Br J Cancer 2005, 92:102-12. [3] Meyer S, J Invest Dermatol 2007, 127:1615-21

ITGB2 Integrin beta 2, CD18 See integrins ITGD, PHY: Heterodimer with ITGD, ITGM, ITGX. [1] http://www.uniprot.org/ uniprot/P05556

MMMP Biomap #87

ITGM and ITGX for details

Beta-1 integrins recognize the sequence RGD in a wide array of ligands. Involved in promoting endothelial cell motility and angiogenesis [1]. See these integrins for more details

ONC: See integrins ITGD, ITGM and ITGX for details

ITGB3 Integrin beta 3, CD61, GPIIIa (platelet glycoprotein IIIa)

See integrins ITGA2B and ITGAV for details

PHY: Heterodimer with ITGA2B and ITGAV. Phosphorylated on tyrosine residues in response to thrombin-induced platelet aggregation [1]

ONC: ITGB3 is targeted by let-7 (a tumor suppressor microRNA) and promotes melanoma invasiveness [2]. See integrins ITGAV, ITGD, ITGM and ITGX for more details

[1] http://www.uniprot.org/ uniprot/P05106. [2] Müller DW, Oncogene 2008, 27:6698-706

ITGB4 Integrin beta 4, CD104 Laminin PHY: Heterodimer with integrin alpha 6 (CD49f/CD104). Laminin receptor on epithelial cells [1]. It plays a critical structural role in the hemidesmosome of epithelial cells [1]. Defects in ITGB4 are a cause of epidermolysis bullosa letalis with pyloric atresia (EBPA) [1]

ONC: Expression of integrin alpha6/beta4 is associated with poor patient prognosis and reduced survival in a variety of human cancers and a key tyrosine (Y1494) in the beta4 integrin regulates multiple signaling pathways important for tumor development and progression [2]. Laminin-332-integrin (VLA-3 and alpha6beta4) interaction is being investigated as a target for cancer therapy [3]

[1] http://www.uniprot.org/uniprot/P23229. [2] Dutta U, Cancer Res 2008, 68:8779-87. [3] Tsuruta D, Curr Med Chem 2008, 15:1968-75

ITGB5 Integrin beta 5 Fibronectin PHY: Heterodimer with integrin alpha V. It recognizes the sequence RGD in its ligand [1]

ONC: -

[1] http://www.uniprot.org/ uniprot/P18084

ITGB6 Integrin beta 6 Fibronectin Cytotactin

PHY: Heterodimer with integrin alpha V. It recognizes the sequence RGD in its ligand [1].

[1] http://www.uniprot.org/ uniprot/P18564. [2] Azare J, Mol Cell Biol 2007, 27:4444-53. [3] Ramos DM, Matrix Biol 2002, 21:297-307

MMMP Biomap #87

Acts as a receptor for viruses such as foot-and-mouth disease virus (FMDV) and coxsackievirus [1]

ONC: Constitutively activated Stat3 induces tumorigenesis and enhances cell motility of prostate epithelial cells through integrin beta 6 [2]. Expression of integrin beta 6 enhances invasive behavior in oral squamous cell carcinoma [3]

ITGB7 Integrin beta 7 E-cadherin VCAM1 MadCAM1 Fibronectin

PHY: Mainly expressed in leukocytes [1]. Integrin alpha-4/beta-7 (Peyer patches-specific homing receptor LPAM-1) is an adhesion molecule that mediates lymphocyte migration and homing to gut-associated lymphoid tissue (GALT). Integrin alpha-4/beta-7 interacts with the cell surface adhesion molecules MadCAM1 which is normally expressed by the vascular endothelium of the gastrointestinal tract. Interacts also with VCAM1 and ECM component fibronectin. Binds to HIV-1 gp120, thereby allowing the virus to enter GALT, which is thought to be the major trigger of AIDS disease. Integrin alpha-E/beta-7 (HML-1) is a receptor for E-cadherin

ONC: -


ITGB8 Integrin beta 8 Fibronectin PHY: Heterodimer with integrin alpha V [1]

ONC: -


JAM1 F11R (F11 receptor), PAM-1 (platelet adhesion molecule), JCAM (junctional cell adhesion molecule), JAMA, JAM-A, CD321

MPDZ PARD3

PHY: Involved in tight junction assembly (epithelial cells), endothelial cell function and platelet adhesion to endothelium. Receptor for orthoreovirus

ONC: Decreased expression in lung squamous carcinoma [1]. In breast cancer HGF disrupts tight junctions by decreasing JAM1 expression [2]

[1] Paschoud S, Mod Pathol 2007, 20:947-54. [2] Martin TA, Cell Biol Int 2004, 28:361-71

JAM2 Junctional adhesion molecule 2, VE-JAM (vascular endothelial JAM), JAM-B,

JAM3 PHY: Involved in tight junction formation. Mainly expressed on high endothelial venules;

[1] Ueki T, Microvasc Res 2008, 75:269-78. [2] Johnson-Léger CA, Blood 2002, 100:2479-86

MMMP Biomap #87

JAMB, CD322 plays a role in lymphocyte homing to secondary lymphoid organs [1,2]

ONC: -

JAM3 Junctional adhesion molecule 3, JAM-C, JAMC

JAM2 PHY: Involved in tight junction formation. Promotes neutrophil transendothelial migration. Participates in cell-cell adhesion distinct from tight junctions [1,2]

ONC: -

[1] Ueki T, Microvasc Res 2008, 75:269-78. [2] Chavakis T, J Biol Chem 2004, 279:55602-8

L1CAM L1 cell adhesion molecule, NCAM-L1, CD171

Neuropilin-1 Integrins

PHY: Defects in L1CAM cause hydrocephalus or other nervous system diseases

ONC: Expression on tumor endothelium mediates selective tumor cell transmigration [1]. Promotes invasiveness of different tumors including melanoma [3], at least in part through ERK stimulation

[1] Issa Y, J Mol Med 2008, Epub ahead of print. [2] Gast D, Oncogene 2008, 27:1281-9. [3] Meier F, Int J Cancer 2006, 119:549-55

LAMP1 Lysosomal associated membrane protein 1, CD107a

Selectins PHY: Presents carbohydrate ligands to selectins [1]. Translocated to the cell surface upon activation. Glycoprotein in human peripheral blood mononuclear cells that mediates cell adhesion to vascular endothelium [2]. Also involved in lysosome/ endosome activities

ONC: Can be expressed by malignant cells, is a ligand of galectin-3 and may influence tumor proliferation and metastasis formation [3]

[1] http://www.uniprot.org/uniprot/P11279. [2] Kannan K, Cell Immunol 1996, 171:10-9. [3] Künzli BM, Cancer 2002, 94:228-39

LAMP2 Lysosomal associated membrane protein 2, CD107b

Selectins PHY: Presents carbohydrate ligands to selectins [1]. Translocated to the cell surface upon activation. Glycoprotein in human peripheral blood mononuclear cells that mediates cell adhesion to vascular endothelium [2]. Also involved in lysosome/ endosome activities

ONC: Can be expressed by malignant cells, is a ligand of galectin-3 and may influence tumor proliferation and metastasis formation

[1] http://www.uniprot.org/uniprot/P13473. [2] Kannan K, Cell Immunol 1996, 171:10-9. [3] Künzli BM, Cancer 2002, 94:228-39

MMMP Biomap #87

[3]

MADCAM1 Mucosal vascular addressin cell adhesion molecule 1, MACAM1

ITG alpha4-beta7 L-selectin

PHY: Cell adhesion leukocyte receptor expressed by mucosal venules (lymphocyte traffic into mucosal tissues, e.g. Peyer patches, intestinal lamina propria during inflammation)

ONC: Tumor-induced expression of addressins on the surface of endothelial cells allows a selective transmigration of Treg cells from peripheral blood to tumor tissues

[1] Nummer D, J Natl Cancer Inst 2007, 99:1188-99

MCAM Melanoma cell adhesion molecule, MUC18, CD146

MCAM PHY: Cohesion of endothelial cells at intercellular junctions. Surface receptor triggering tyrosine phosphorylation of FYN and PTK2. Detected in endothelial cells in vascular tissue throughout the body

ONC: Promotes invasiveness and in vivo metastasis of melanoma cells [1,2]. Associated with advanced stages in melanoma patients [3]. May allow melanoma cells to interact with cellular elements of the vascular system, thereby enhancing hematogenous tumor spread

[1] Wu GJ, Mol Cancer Res 2008, 6:1666-77. [2] Staquicini FI, Cancer Res 2008, 68:8419-28. [3] Rapanotti MC, Br J Dermatol 2008, Epub ahead of print

MTDH Metadherin, LYRIC, AEG-1 (astrocyte elevated gene 1)

? PHY: Tight junction protein

ONC: Overexpressed in more than 40% of breast cancers, associated with poor clinical outcomes; activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer [1,2]. promote tumor cell migration and invasion through activation of NFkB [3] and survival through PI3K/AKT stimulation [4] and FOXO3a inhibition [5]. AEG-1 expression is elevated also in subsets of melanoma cells [6]

[1] Hu G, Cancer Cell 2009, 15:9-20. [2] Brown DM, Cancer Cell 2004, 5:365-74. [3] Sarkar D, Cancer Res 2008, 68:1478-84. [4] Lee SG, Oncogene 2008, 27:1114-21. [5] Kikuno N, Oncogene 2007, 26:7647-55. [6] Emdad L, Cancer Res 2006, 66:1509-16

MUC1 Mucin 1, Episialin, CD227, PUM, PEM ICAM PHY: Acts as a heterodimeric complex of two subunits, MUC1-alpha and MUC1-beta,

[1] http://www.uniprot.org/uniprot/P15941. [2] Singh R, Cancer Biol Ther 2007, 6:481-6. [3] Tang CK, Expert Rev Vaccines 2008, 7:963-75

MMMP Biomap #87

MUCINS Mucins are high-molecular weight epithelial glycoproteins with a high content of clustered oligosaccharides O-glycosidically linked to tandem repeat peptides rich in threonine, serine, and proline. There are two structurally and functionally distinct classes of mucins: secreted gel-forming mucins (MUC2, MUC5AC, MUC5B, and MUC6) and transmembrane mucins (MUC1, MUC3A, MUC3B, MUC4, MUC12, MUC17), although the products of some MUC genes do not fit well into either class (MUC7, MUC8, MUC9, MUC13, MUC15, MUC16). Deregulation of mucin expression and or glycosylation can be found in many tumor types. The O-glycosidically linked oligosaccharides of mucins can be described in terms of core type (e.g. Tn antigen [GalNAcalphaThr/Ser], TF antigen [Galbeta3GalNAc], sialyl Tn [NeuAcalpha6GalNAc]), backbone type, and peripheral structures. Cancer-related mucins differ from those of healthy tissues mainly in core and peripheral carbohydrate structures, which are being investigated as diagnostic and prognostic markers, as well as targets for immunotherapy. core structures:. REFERENCES: [1] Carraway KL, Curr Top Dev Biol 2007, 78:1-22. [2] Singh AP, Lancet Oncol 2008, 9:1076-85. [3] Yonezawa S, Proteomics 2008, 8:3329-41

derived from a single gene. Involved in epithelial cell adhesion, may provide a protective layer on epithelial cells. Modulates signaling in ERK, SRC and NFkB pathways. Forms a MUC1/GRB2/SOS1 complex involved in RAS signaling. Binds, together with KLF4, the PE21 promoter element of P53 and represses P53 activity. The cytoplasmic tail interacts with several proteins such as SRC, CTNNB1 and ERB family members. Interaction with the SH2 domain of CSK decreases interaction with GSK3B. Interacts with CTNNB1/beta-catenin and JUP/gamma-catenin and promotes cell adhesion. Interaction with JUP/gamma-catenin is induced by heregulin. Binds PRKCD, ERBB2, ERBB3 and ERBB4. Heregulin (HRG) stimulates the interaction with ERBB2 and, to a much lesser extent, the interaction with ERBB3 and ERBB4 [1]

ONC: Overexpressed in adenocarcinomas and hematological cancers [2]. Interaction, via the tandem repeat region, with domain 1 of ICAM1 is implicated in carcinoma cell migration and metastasis [1]. Is being

MMMP Biomap #87

evaluated as tumor antigen for anticancer immunotherapy [3]

MUC2 Mucin 2 ? PHY: Secreted glycoprotein. Coats the epithelia of the intestines, airways, and other mucus membrane-containing organs. Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces [1]

ONC: -


MUC3A Mucin 3A ? PHY: See MUC2

ONC: -

-

MUC3B Mucin 3B ? PHY: See MUC2

ONC: -

-

MMMP Biomap #87

MUC4 Mucin 4 ? PHY: A heterodimeric complex of two subunits, ASGP-1 and ASGP-2, derived from a single gene. It is produced by multiple epithelia in both membrane and soluble forms and serves as a protective agent for the epithelia Expressed in the thymus, thyroid, lung, trachea, esophagus, stomach, small intestine, colon, testis, prostate, ovary, uterus, placenta, and mammary and salivary glands

ONC: Ability to promote tumor growth may be mainly due to repression of apoptosis as opposed to proliferation. Seems to alter cellular behavior through both anti-adhesive effects on cell-cell and cell-extracellular matrix interactions and in its ability to act as an intramembrane ligand for ErbB2 (through its EGF-like domains). The transmembrane subunit ASGP-2 acts as an intramembrane ligand and activator for the receptor tyrosine kinase ErbB2. Formation of this ligand-receptor complex is proposed to repress apoptosis in epithelial and cancer cells

[1] Bafna S, Cancer Res 2008, 68:9231-8. [2] Ponnusamy MP, Br J Cancer 2008, 99:520-6. [3] Chaturvedi P, Cancer Res 2008, 68:2065-70. [4] Chaturvedi P, FASEB J 2008, 22:966-81

MUC5AC Mucin 5AC ? PHY: See MUC2

ONC: -

-

MUC5B Mucin 5B ? PHY: See MUC2

ONC: -

-

MUC6 Mucin 6 ? PHY: See MUC2

ONC: -

-

MUC7 Mucin 7 ? PHY: See MUC2

ONC: -

-

MUC12 Mucin 12 ? PHY: Involved in epithelial cell protection, adhesion modulation, and signaling. May be involved in epithelial cell growth regulation. Stimulated by both cytokine TNF-alpha and TGF-beta in intestinal epithelium. Ubiquitous,

[1] http://www.uniprot.org/uniprot/Q9UKN1

MMMP Biomap #87

with higher expression in colon [1]

ONC: -

MUC13 Mucin 13 ? PHY: ?

ONC: -

-

MUC15 Mucin 15 ? PHY: May play a role in the cell adhesion to the extracellular matrix [1]

ONC: Downregulated in metastatic as compared to primary melanoma [2]

[1] http://www.uniprot.org/uniprot/Q8N387. [2] Riker AI, BMC Med Genomics 2008, 1:13

MUC16 Mucin 16, CA125 Mesothelin PHY: Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. Binding to MSLN (mesothelin) mediates heterotypic cell adhesion. May be secreted into the extracellular space following the phosphorylation of the intracellular C-terminus which induces the proteolytic cleavage of the extracellular domain. Expressed in corneal and conjunctival epithelia [1]

ONC: Overexpressed in ovarian cancer (is used in the clinical practice as a serum marker). Interaction with MSLN (normally expressed by mesothelial cells) likely explains ovarian cancer tropism for peritoneum.

[1] http://www.uniprot.org/uniprot/Q8WXI7

MUC17 Mucin 17 ? PHY: Expressed almost exclusively in the intestine. Probably plays a role in maintaining homeostasis on mucosal surfaces [1]

ONC: Highly expressed in pancreatic adenocarcinoma tissue (at protein level). Expression is not detectable in normal pancreas, in pancreatitis or in cell lines derived from other cancers [1]

[1] http://www.uniprot.org/uniprot/Q685J3

MUC19 Mucin 19 ? PHY: Expressed corneal epithelial cells, conjunctival goblet and epithelial cells and lacrimal gland cells, may function in ocular

[1] http://www.uniprot.org/uniprot/Q7Z5P9

MMMP Biomap #87

mucus homeostasis [1]

ONC: -

MUC20 Mucin 20 ? PHY: Highly expressed in kidney, moderately in placenta, lung, prostate, liver, and digestive system. May regulate c-MET signaling cascade by decreasing hepatocyte growth factor (HGF)-induced transient MAPK activation; blocks GRB2 recruitment to c-MET thus suppressing the GRB2-RAS pathway; inhibits HGF-induced proliferation of MMP1 and MMP9 expression [1]. Oligomerization is required for interaction with c-MET

ONC: -

[1] Higuchi T, Mol Cell Biol 2004, 24:7456-68

MUC21 Mucin 21, Epiglycanin ? PHY: Expressed in lung, large intestine, thymus, and testis. Expressed in normal and malignant bronchial epithelial cells

ONC: Could be a marker of lung adenocarcinoma [1]

[1] Itoh Y, Glycobiology 2008, 18:74-83

MUPCDH Mucin-like protocadherin, MUCDHL ? PHY: Acts as a calcium-dependent cell adhesion protein. Highest expression in kidney, liver, colon and small intestine [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9HBB8

NCAM1 Neural cell adhesion molecule 1, NCAM, CD56

NCAM1 PHY: Involved in neuron-neuron adhesion, neurite fasciculation and outgrowth of neurites. First described in neurons, is also expressed in a wide variety of non-neuronal cell types

ONC: Expression is deregulated in different cancer types. However, NCAM can exert both a positive and a negative effect on cancer progression depending on the tumor context [1]

[1] Zecchini S, Neurochem Res 2008, Epub ahead of print

NCAM2 Neural cell adhesion molecule 2, NCAM21, N-CAM2, OCAM (olfactory CAM), RNCAM

NCAM2 PHY: Expressed most strongly in adult and fetal brain. May play important roles in selective fasciculation and zone-to-zone

[1] Kulahin N, Neurochem Res 2008, Epub ahead of print

MMMP Biomap #87

projection of the primary olfactory axons [1]

ONC: -

Nectin 1 PVRL1 (poliovirus receptor related 1), HVEC (Herpes virus entry mediator C), CD111

Nectins PHY: Promotes cell-cell contacts by forming homophilic or heterophilic trans-dimers. Heterophilic interactions: can form trans-heterodimers with PVRL3/nectin-3 and with PVRL4/nectin-4 [1]

ONC: Calcium depletion enhances nectin-1 expression and herpes oncolytic therapy of squamous cell carcinoma [2]

[1] Takai Y, Nat Rev Mol Cell Biol 2008, 9:603-15. [2] Yu Z, Cancer Gene Ther 2007, 14:738-47

Nectin 2 PVRL2 (poliovirus receptor related 2), CD112

Nectins PHY: Can form trans-heterodimers with PVRL3/nectin-3. Interacts with CD226. Receptor for alpha herpesvirus (HSV-1, HSV-2 and pseudorabies virus) entry into cells

ONC: -


Nectin 3 PVRL3 (poliovirus receptor related 3), CD113

Nectins PHY: Plays a role in cell-cell adhesion through heterophilic trans-interactions with nectin-like proteins or nectins, such as trans-interaction with PVRL2/nectin-2 at Sertoli-spermatid junctions. Cis- and trans-homodimer. Can form trans-heterodimers with PVRL1/nectin-1 and PVRL2/nectin-2 [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9NQS3

Nectin 4 PVRL4 (poliovirus receptor related 4) Nectins PHY: Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with PVRL2/nectin-1

ONC: Nectin-4 is a new histological and serological tumor associated marker for breast cancer [2]

[1] http://www.uniprot.org/uniprot/Q96NY8. [2] Fabre-Lafay S, BMC Cancer 2007, 7:73

NRCAM NgCAM related cell adhesion molecule, Nr-CAM, Bravo

NRCAM Neurofascin RPTPbeta [1]

PHY: Mainly expressed in central nervous system (CNS). Cell adhesion, ankyrin-binding protein involved in neuron-neuron adhesion

ONC: Is a target of SKI (inhibitor of TGF-beta

[1] Grumet M, Cell Tissue Res 1997, 290:423-8. [2] Chen D, Cancer Res 2003, 63:6626-34. [3] Conacci-Sorrell ME, Genes Dev 2002, 16:2058-72. [4] Conacci-Sorrell M, Cancer Res 2005, 65:11605-12

MMMP Biomap #87

pathway and stimulator of WNT/beta-catenin pathway) [2] and is associated with melanoma cell survival, growth, motility and transformation [3]. Metalloprotease-mediated shedding of NRCAM is a route for NRCAM mediated oncogenesis [4]

Occludin OCLN TJP1 PHY: Plays a role in the formation and regulation of the tight junction paracellular permeability barrier. Can induce adhesion when expressed in cells lacking tight junctions. Localized at tight junctions of both epithelial and endothelial cells. Highly expressed in kidney [1]

ONC: In renal cell carcinoma (RCC), VHL loss leads to epithelial mesenchymal transition (EMT) by downregulation not only of E-cadherin expression (adherens junction) but also occludin and claudin-1 (tight junction) [2]. Occludin-mediated premature senescence is a fail-safe mechanism against tumorigenesis in breast carcinoma cells [3]

[1] http://www.uniprot.org/uniprot/Q16625. [2] Harten SK, Mol Biol Cell 2008, Epub ahead of print. [3] Osanai M, Cancer Sci 2007, 98:1027-34

OMD Osteomodulin, Osteoadherin ITG alpha V-beta3 PHY: May be implicated in biomineralization processes. Has a function in binding of osteoblasts via integrin alpha V-beta 3

ONC: -


OPCML Opioid binding protein/cell adhesion molecule-like, OPCM, OBCAM (opioid binding cell adhesion molecule)

Opioids OPCML LSAMP [1]

PHY: Belongs to the IgLON (OPCML, LSAMP, NEGR1 and HNT) family of glycosyl phosphatidyl inositol (GPI)-anchored cell adhesion molecules (CAM) that are highly expressed in the nervous system

ONC: Is considered a tumor suppressor for multiple carcinomas and lymphomas with frequently epigenetic inactivation [2,3]. Ectopic expression leads to inhibition of both anchorage-dependent and -independent growth of carcinoma cells [2]

[1] Lodge AP, Brain Res Mol Brain Res 2000, 82:84-94. [2] Cui Y, PLoS ONE 2008, 3:e2990. [3] Mei FC, FASEB J 2006, 20:497-9

MMMP Biomap #87

PCDH1 Protocadherin 1, PC42 ?

PROTOCADHERINS (PCDHs) Protocadherins are the largest subgroup within the cadherin superfamily, usually contain 6 to 7 cadherin repeats in their extracellular domain, are predominantly expressed in the nervous system, lack an interface for homophilic adhesiveness (found in classical cadherins) and present loop structures absent in other members of the cadherin superfamily. They are involved in both cell adhesion and cell signaling. REFERENCES: [1] Morishita H, Curr Opin Cell Biol 2007, 19:584-92. [2] Takeichi M, Nat Rev Neurosci 2007, 8:11-20

PHY: May be involved in cell-cell interaction processes and in cell adhesion. Highly expressed in the brain and neuro-glial cells. Highest expression in adults [1]. Belongs to the delta-protocadherins that comprise

PCDH7, PCDH8, PCDH9, PCDH10, PCDH11, PCDH17, PCDH18, PCDH19, PCDHX and PCDHY [2]

ONC: -

[1] http://www.uniprot.org/uniprot/Q08174. [2] Redies C, Cell Mol Life Sci 2005, 62:2840-52

PCDH7 Protocadherin 7, BH-PCDH (brain heart) ? PHY: Expressed predominantly in brain and heart and at lower levels in various other tissues [1]

ONC: Upregulated in androgene independent prostate carcinoma [2]

[1] http://www.uniprot.org/uniprot/O60245. [2] Singh AP, Cancer Lett 2008, 259:28-38

PCDH8 Protocadherin 8, PAPC, ARCADLIN ? PHY: Potential calcium-dependent cell-adhesion protein

ONC: Candidate tumor suppressor of breast cancer [1]

[1] Yu JS, Oncogene 2008, 27:4657-65

PCDH9 Protocadherin 9 ? PHY: Potential calcium-dependent cell-adhesion protein

ONC: Candidate tumor suppressor gene of glioblastoma [1]

[1] de Tayrac M, Genes Chromosomes Cancer 2009, 48:55-68

PCDH10 Protocadherin 10, Protocadherin-OL ? PHY: Potential calcium-dependent cell-adhesion protein. Moderately expressed in all regions of the brain examined, as well as in testis and ovary, and low expression in all other tissues tested [1]

ONC: Tumor suppressor gene whose methylation is associated with poor prognosis

[1] http://www.uniprot.org/uniprot/Q9P2E7. [2] Yu J, Gastroenterology 2008, Epub ahead of print. [3] Ying J, Oncogene 2006, 25:1070-80. [4] Ying J, Br J Haematol 2007, 136:829-32

MMMP Biomap #87

in patients with gastric cancer [2]. Epigenetically silenced (by methylation) also in other carcinomas and multiple hematologic malignancies [4]

PCDH11X Protocadherin 11 X- linked, PCDHX, Protocadherin-S

? PHY: Potential calcium-dependent cell-adhesion protein. Expressed strongly in fetal brain and brain (cortex, amygdala, thalamus, substantia nigra, hippocampus, caudate nucleus and corpus callosum) [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9BZA7

PCDH11Y Protocadherin 11 Y- linked, PCDHY, PCDH-PC (prostate cancer)

? PHY: Potential calcium-dependent cell-adhesion protein. Interacts with CTNNB1. Expressed strongly in fetal brain and brain (cortex, amygdala, thalamus, substantia nigra, hippocampus, caudate nucleus and corpus callosum). Expressed in apoptosis-resistant cells. A chromosomal aberration involving PCDH11Y is a cause of multiple congenital abnormalities including severe bilateral vesico-ureteral reflux [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9BZA8

PCDH12 Protocadherin 12, VE-cadherin 2 ? PHY: Expressed in highly vascularized tissues including the heart and placenta, but most tissues contain a low level of expression. Prominent expression in the spleen. Cellular adhesion molecule that may play an important role in cell-cell interactions at interendothelial junctions. Promotes homotypic calcium dependent aggregation and adhesion and clusters at intercellular junctions. Unable to bind to catenins, weakly associates with the cytoskeleton [1,2]

ONC: -

[1] Rampon C, Physiol Genomics 2008, 34:193-204. [2] http://www.uniprot.org/uniprot/Q9NPG4

PCDH15 Protocadherin 15, DFNB23 ? PHY: Calcium-dependent cell-adhesion protein. Expressed in brain, lung, kidney, spleen and testis. Essential for maintenance of normal retinal and cochlear function. Defects in PCDH15 are the cause of Usher

[1] http://www.uniprot.org/uniprot/Q96QU1. [2] Rouget-Quermalet V, Oncogene 2006, 25:2807-11

MMMP Biomap #87

syndrome type 1F (USH1F, association of retinitis pigmentosa and sensorineural deafness) and DFNB23 (non-syndromic sensorineural deafness recessive type 23) [1]

ONC: whereas protocadherins are absent from the surface of normal hematopoietic cells, we describe, for the first time, that PCDH15 is expressed in cytotoxic tumor-derived T- and NK-cell lines as well as in biopsies of nasal NK/T-cell lymphomas [2]

PCDH17 Protocadherin 17, PCDH68 ? PHY: Potential calcium-dependent cell-adhesion protein [1]

ONC: -


PCDH18 Protocadherin 18, PCDH68L ? PHY: Potential calcium-dependent cell-adhesion protein. Expressed in all tissues, with highest expression in lung and ovary [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9HCL0

PCDH19 Protocadherin 19 ? PHY: Potential calcium-dependent cell-adhesion protein. Moderately expressed in all regions of the brain examined, with lowest levels found in the cerebellum. Moderate expression is also found in ovary, and low expression in all other tissues tested. Also detected in primary skin fibroblast. Defects in PCDH19 are the cause of epilepsy, female-restricted, with mental retardation (EFMR) [1,2]

ONC: -

[1] http://www.uniprot.org/uniprot/Q8TAB3. [2] Dibbens LM, Nat Genet 2008, 40:776-81

PCDH20 Protocadherin 20, PCDH13 ? PHY: Potential calcium-dependent cell-adhesion protein

ONC: Candidate tumor suppressor gene frequently silenced by epigenetic mechanism (promoter hypermethylation) in non-small-cell lung cancer (NSCLC); its methylation status correlates with patients survival [1]

[1] Imoto I, Cancer Res 2006, 66:4617-26

PCDH21 Protocadherin 21, PR-cadherin ? PHY: Potential calcium-dependent cell- [1] http://www.uniprot.org/uniprot/Q96JP9. [2]

MMMP Biomap #87

(photoreceptor) adhesion protein. May be required for the structural integrity of the outer segment of photoreceptor cells [1]. Candidate gene for human retinal dystrophies [2]

ONC: -

Bolz H, Mol Vis 2005, 11:929-33

PCDH24 Protocadherin 24, PCDH LKC (liver kidney colon)

? PHY: Role in contact inhibition at the lateral surface of epithelial cells. Highly expressed in liver, kidney and colon [1]

ONC: Downregulated in liver and colon cancers [2], where it acts as a tumor suppressor gene by mediating contact inhibition [2]

[1] http://www.uniprot.org/uniprot/Q9BYE9. [2] Okazaki N, Carcinogenesis 2002, 23:1139-48

PCDHA1 Protocadherin alpha 1 ? PHY: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain [1]. Belongs to the clustered protocadherin subfamily of the cadherin superfamily. Clustered PCDH are predominantly expressed in the nervous system and are substructured into three distinct gene arrays in mammals: Pcdh-alpha, Pcdh-beta, and Pcdh-gamma. Pcdh-alpha proteins interact with ITGB1 to promote cell adhesion [2]

ONC: Changes in DNA methylation patterns are a common characteristic of cancer cells; recent studies suggest that DNA methylation affects not only discrete genes, but it can also affect large chromosomal regions potentially leading to LRES ( long-range epigenetic events); in breast carcinoma, one example of a newly discovered agglomerate of hypermethylated regions associated with gene silencing involves the protocadherin gene family clusters on chromosome 5 (PCDHA, PCDHB, and PCDHG) [3]

[1] http://www.uniprot.org/uniprot/Q9Y5I3. [2] Hirayama T, Curr Opin Neurobiol 2006, 16:336-42. [3] Novak P, Cancer Res 2008, 68:8616-25

PCDHA2 Protocadherin alpha 2 ? PHY: See PCDHA1 for details

ONC: See PCDHA1 for details


MMMP Biomap #87




PCDHA4 Protocadherin alpha 4, CNR1 ? PHY: See PCDHA1 for details


[1] http://www.uniprot.org/uniprot/Q9UN74


















[1] http://www.uniprot.org/uniprot/Q9Y5I2










PCDHB1 Protocadherin beta 1 ? PHY: See PCDHA1 for details


[1] http://www.uniprot.org/uniprot/Q9Y5F3

MMMP Biomap #87



[1] http://www.uniprot.org/uniprot/Q9Y5E7
















PCDHB8 Protocadherin beta 8, PCDH3I ? PHY: See PCDHA1 for details



PCDHB9 Protocadherin beta 9, PCDH3H ? PHY: See PCDHA1 for details






PCDHB11 Protocadherin beta 11, Cadherin ME2 ? PHY: See PCDHA1 for details









MMMP Biomap #87







PCDHB16 Protocadherin beta 16, Cadherin ME1 ? PHY: See PCDHA1 for details


[1] http://www.uniprot.org/uniprot/Q9NRJ7

PCDHGA1 Protocadherin gamma subfamily A 1 ? PHY: See PCDHA1 for details











[1] http://www.uniprot.org/uniprot/Q9Y5G9

PCDHGA5 Protocadherin gamma subfamily A 5, Cadherin ME3

? PHY: See PCDHA1 for details















MMMP Biomap #87





ONC: Epigenetic silencing of the protocadherin family member PCDH-gamma-A11 in astrocytomas [1]. See PCDHA1 for more details

[1] Waha A, Neoplasia 2005, 7:193-9

PCDHGA12 Protocadherin gamma subfamily A 12, CDH21

? PHY: See PCDHA1 for details

ONC: Belongs to a gene expression signature that predicts survival of patients with non-small cell lung cancer (NSCLC) [1]. See PCDHA1 for more details

[1] Lu Y, PLoS Med 2006, 3:e467

PECAM1 Platelet and endothelial cell adhesion molecule, CD31, PECAM-1

PECAM1 (mainly), integrin aVb3, CD38, CD177

PHY: Expressed by endothelial cells (mainly at intercellular junctions); expressed to different degrees on leukocytes and platelets. Besides adhesive properties, PECAM1 mediates cell signaling in inflammation, angiogenesis, platelet function, thrombosis and leukocyte migration through venular walls [1]. Binds tyrosine-phosphorylated b-catenin and modulates b-catenin localization. Potent suppressor of Bax-mediated apoptosis

ONC: Used to measure tumor microvascular density (MVD), which correlates with prognosis [2] (although in melanoma conflicting results are reported [3]).

[1] Woodfin A, Arterioscler Thromb Vasc Biol 2007, 27:2514-23. [2] Nico B, Histol Histopathol 2008, 23:601-7. [3] Wobser M, Arch Dermatol Res 2006, 297:352-7. [4] Massi D, Virchows Arch 2002, 440:22-8

Plakoglobin JUP (junctional plakoglobin), DP3 (desmoplakin 3), DPIII, PDGB, PKGB, CTNNG (catenin gamma)

Desmoglein, desmocollin

PHY: Desmosome formation (see the above Figure, in the Desmocollin box). Acts as a homodimer. Interacts with MUC1. Belongs to the beta-catenin family. The presence of plakoglobin in both desmosomes and intermediate junctions suggests it plays a central role in submembranous plaques. Defects in JUP are the cause of Naxos disease (NXD) - an autosomal recessive disorder combining diffuse non-epidermolytic palmoplantar keratoderma with

[1] http://www.uniprot.org/uniprot/P14923. [2] Kanazawa Y, Anticancer Res 2008, 28(2A):655-64. [3] Shafiei F, Oncogene 2008, 27:2602-12. [4] Rieger-Christ KM, Br J Cancer 2005, 92:2153-9. [5] Williams BO, Oncogene 2000, 19:5720-8

MMMP Biomap #87

arrhythmogenic right ventricular dysplasia - and the cause of familial arrhythmogenic right ventricular dysplasia type 12 (ARVD12) [1]

ONC: Down-regulation of plakoglobin in soft tissue sarcoma is associated with a higher risk of pulmonary metastasis [2]. Autocrine growth hormone (GH)-stimulated increases in DNMT3A and DNMT3B expression mediate repression of plakoglobin gene transcription by direct hypermethylation of its promoter and consequent oncogenic effects in mammary carcinoma cells [3]. Restoration of plakoglobin expression in bladder carcinoma cell lines suppresses cell migration and tumorigenic potential [4]. Beta-catenin and its close homologue plakoglobin (gamma-catenin) are major constituents of submembranal cell-cell adhesion sites; in addition, beta-catenin is a key component in the canonical WNT pathway. Aberrantly activated beta-catenin signaling contributes to cancer progression by inducing [in complex with lymphocyte enhancer factor (LEF)/T-cell factor (TCF)] the transcription of proliferation-related genes such as cyclin D1 and c-Myc. Plakoglobin can also activate LEF/TCF-mediated transcription [5]

PUNC Putative neuronal cell adhesion molecule - PHY: ?

ONC: Along with MARCO and SPARC, appears to correlate with prognosis of breast cancer patients [1]

[1] Bergamaschi A, J Pathol 2008, 214:357-67

SDK1 Sidekick homolog 1 (cell adhesion molecule)

-

- PHY: Cell adhesion protein that guides axonal terminals to specific synapses in developing neurons

ONC: -

[1] Yamagata M, Cell 2002, 110: 649-60

Selectin-E Selectin (endothelial), E-selectin, SELE, ESEL, ELAM (endothelial leukocyte adhesion molecule), CD62E

SELPLG CD44 [2]

PHY: Key role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG. Involved in

[1] Tremblay PL, Cancer Res 2008, 68:5167-76. [2] Zen K, PLoS ONE 2008, 3:e1826. [3] Hakomori S, Proc Natl Acad Sci USA 2002, 99:10231-3. [4] Fukuda MN, Cancer Res 2000,

MMMP Biomap #87

atherosclerosis

ONC: Promotes diapedesis, the passage of circulating tumor cells (CTC) across the endothelium (a critical determinant of metastasis formation) [1,2]. The carbohydrate determinant sialyl Lewis(a) is known to be expressed strongly on cancers of the digestive organs (this carbohydrate antigen, known as CA19-9, is the most frequently applied serum tumor marker for diagnosis of cancers in the digestive organs) and to serve as a ligand for vascular E-selectin in hematogenous metastasis of cancers [3]. A peptide mimic of E-selectin ligand inhibits sialyl Lewis X-dependent lung colonization of murine melanoma cells [4]. Low expression of selectin-E in melanoma specimens might underlie insufficient recruitment of cytotoxic T lymphocytes and thus limit the effectiveness of immunotherapy regimens [5]

60:450-6. [5] Weishaupt C, Clin Cancer Res 2007, 13:2549-56

Selectin-L Selectin (leukocyte), L-selectin, SELL, LSEL, LAM1, Leu-8, Lyam-1, PLNHR, CD62L, LNHR (lymph node homing receptor)

SELPLG CD44 [1] CD34

PHY: Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes. Key role in leukocyte migration during inflammation [2]

ONC: L-selectin, along with E- or P-selectin, mediates cell tethering and rolling interactions through the recognition of sialo-fucosylated Lewis carbohydrates expressed on structurally diverse protein-lipid ligands on circulating leukocytes or tumor cells [2] (including melanoma [3])

[1] Hanley WD, FASEB J 2006, 20:337-9. [2] Barthel SR, Expert Opin Ther Targets 2007, 11:1473-91. [3] Chen S, Methods Enzymol 2006, 416:371-80

Selectin-P Selectin (platelet), PSEL (P-selectin), PADGEM, GMP140 (granule membrane protein 140), CD62P, LECAM3 (leukocyte & endothelial cell adhesion molecule 3)

SELPLG CD44 [1]

PHY: Calcium-dependent receptor for myeloid cells that binds to carbohydrates on neutrophils and monocytes. Mediates the interaction of activated endothelial cells or platelets with leukocytes

ONC: During cancer metastasis the formation of platelet-tumor cell aggregates in the circulation facilitates immune evasion and the

[1] Thomas SN, J Biol Chem 2008, 283:15647-55. [2] Borsig L, Expert Rev Anticancer Ther 2008, 8:1247-55. [3] Hostettler N, FASEB J 2007, 21:3562-72. [4] Lee DY, Clin Cancer Res 2008, 14:2841-9. [5] Weishaupt C, Clin Cancer Res 2007, 13:2549-56

MMMP Biomap #87

microvascular arrest of tumor cells at distant sites: adhesion molecules such as integrins and P-selectin are involved in these platelet-tumor cell interactions [2]. Selectin-specific heparin derivatives inhibit metastasis formation in mouse melanoma models [3,4]. Low expression of selectin-E in melanoma specimens might underlie insufficient recruitment of cytotoxic T lymphocytes and thus limit the effectiveness of immunotherapy regimens [5]

SELPLG Selectin-P ligand, CD162, PSGL-1 (P-selectin glycoprotein 1)

Selectin-E Selectin-L Selectin-P

PHY: A SLe(x)-type glycan that mediates recruitment and rolling of leukocytes over vascular surfaces during the initial steps of inflammation through calcium-dependent interaction with selectins (through their lectin/EGF domains). These interactions require sialyl Lewis X glycan modification of SELPLG

ONC: -

[1] Veldman GM, J Biol Chem 1995, 270:16470-5

SIGLEC1 Sialic acid-binding Ig-like lectin 1, CD169, sialoadhesin

Sialic acid-containing molecules

PHY: Macrophage-restricted adhesion molecule that mediates sialic-acid dependent binding to lymphocytes, granulocytes, monocytes, NK cells, B-cells and CD8+ T-cells [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9BZZ2

SIGLEC5 Sialic acid-binding Ig-like lectin 5, CD170, OBBP2 (obesity-binding protein 2), CD33L2 (CD33 like 2)


PHY: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Expressed by monocytic/myeloid lineage cells [1]

ONC: -


SIGLEC6 Sialic acid-binding Ig-like lectin 6, CD327, OBBP1 (obesity-binding protein 1), CD33L1 (CD33 like 1)


PHY: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Expressed at high levels in placenta (cyto- and syncytiotrophoblastic cells) and at lower levels in spleen, peripheral blood leukocytes (predominantly B-cells) and small


MMMP Biomap #87

intestine [1]

ONC: -

SIGLEC7 Sialic acid-binding Ig-like lectin 7, CD328, AIRM1 (adhesion inhibitory receptor molecule 1)


PHY: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Contains a cytoplasmic immunoreceptor tyrosine-based inhibitor motif (ITIM): if phosphorylated this motif can bind the SH2 domain of phosphatases. In the immune response, CD328 acts as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatases that block signal transduction through dephosphorylation of signaling molecules. Mediates inhibition of natural killer cells cytotoxicity [1]

ONC: Like CD33, SIGLEC7 blocks proliferation of normal and leukemic myeloid cells [2]. Loss of disialyl Lewis(a), the ligand for Siglec-7, is associated with increased sialyl Lewis (a) (the commonly used CA19.9 serum marker) expression on human colon cancer [3]

[1] http://www.uniprot.org/uniprot/Q9Y286. [2] Mingari MC, Immunol Rev 2001, 181:260-8. [3] Miyazaki K, Cancer Res 2004, 64:4498-505

SIGLEC8 Sialic acid-binding Ig-like lectin 8, SAF2 (sialoadhesin family member 2)


PHY: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Contains a cytoplasmic immunoreceptor tyrosine-based inhibitor motif (ITIM) (see SIGLEC7) [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q9NYZ4

SIGLEC9 Sialic acid-binding Ig-like lectin 9, CD329 Sialic acid-containing molecules

PHY: Putative adhesion molecule that mediates sialic-acid dependent binding to cells [1]

ONC: CD33 (Siglec-3) is expressed on most acute myeloid leukemia (AML) cells and is currently being exploited as a therapeutic target: SIGLEC9, a CD33-related molecule, was the most highly expressed among SIGLECs, while it was absent from normal bone marrow myeloid progenitors [2]

[1] http://www.uniprot.org/uniprot/Q9Y336. [2] Biedermann B, Leuk Res 2007, 31:211-20

MMMP Biomap #87

SIGLEC10 Sialic acid-binding Ig-like lectin 10, SLG2 Sialic acid-containing molecules

PHY: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. In the immune response, may act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules. Expressed by peripheral blood leukocytes (eosinophils, monocytes and a natural killer cell subpopulation) [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q96LC7

SIGLEC11 Sialic acid-binding Ig-like lectin 11 Sialic acid-containing molecules

PHY: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q96RL6

SIGLEC12 Sialic acid-binding Ig-like lectin 12, SIGLECL1


PHY: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. The short isoform is highly expressed in spleen, small intestine and adrenal gland; it is lower expressed in thyroid, placenta, brain, stomach, bone marrow, spinal chord and beast. The long isoform is highly expressed in spleen, small intestine and bone marrow; it is lower expressed in thyroid, placenta, thymus, trachea, stomach, lung, adrenal gland, fetal brain and testis. Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q96PQ1

SIGLEC14 Sialic acid-binding Ig-like lectin 14 Sialic acid-containing PHY: Putative adhesion molecule. Sialic acid- [1] http://www.uniprot.org/uniprot/Q08ET2

MMMP Biomap #87

molecules binding paired receptor which may activate associated receptors. Interacts with TYROBP. Mainly expressed in hematopoietic tissues including bone marrow, spleen and fetal liver [1]

ONC: -

SIGLEC15 Sialic acid-binding Ig-like lectin 15, CD33L3 (CD33 like 3)


PHY: Binds sialylated glycoproteins. Interacts with TYROBP and HCST. Expressed in macrophage and/or dendritic cells of spleen and lymph nodes [1]

ONC: -

[1] http://www.uniprot.org/uniprot/Q6ZMC9

Syndecan 1 SDC1, SYND1, CD138 Miscellany PHY: Cell surface proteoglycan that bears both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix. Anchorage of cells to "heparin"-binding domains that are prevalent in extracellular matrix (ECM) components is thought to occur primarily through the syndecans. Syndecans interact with a wide variety of molecules, including growth factors, cytokines, proteinases, adhesion receptors and extracellular matrix components, through their heparan sulfate chains. Recent studies indicate that these interactions not only regulate key events in development and homeostasis, but also key mechanisms of the host inflammatory response and tissue injury repair [1,2]

ONC: In some cancers, syndecan expression has been shown to regulate tumor cell function (e.g. proliferation, adhesion, and motility) and serve as a prognostic marker for tumor progression and patient survival [3]. fibroblast-derived MT1-MMP cleaves Sdc1 at the fibroblast surface, leading to paracrine growth stimulation of breast carcinoma cells by Sdc1 ectodomain [4]. A significant correlation was found between the loss of syndecan-1 epithelial expression and the

[1] Bartlett AH, Mol Cells 2007, 24:153-66. [2] Morgan MR, Nat Rev Mol Cell Biol 2007, 8:957-69. [3] Fears CY, Matrix Biol 2006, 25:443-56. [4] Su G, Cancer Res 2008, 68:9558-65. [5] Loussouarn D, Br J Cancer 2008, 98:1993-8. [6] Nikolova V, Carcinogenesis 2009, Epub ahead of print

MMMP Biomap #87

syndecan-1 stromal expression with high grade of breast cancer [5]. Soluble- and membrane-bound forms of Syndecan-1 play different roles at different stages of breast cancer progression: proteolytic conversion of Syndecan-1 from a membrane-bound into a soluble molecule marks a switch from a proliferative to an invasive phenotype [6]

Syndecan 2 SDC2, SYND2, HSPG1 (heparan sulfate proteoglycan 1), fibroglycan

Miscellany PHY: The syndecans comprise a family of cell surface heparan sulfate proteoglycans exhibiting complex biological functions involving the interaction of heparan sulfate side chains with a variety of soluble and insoluble heparin-binding extracellular ligands [1]

ONC: Syndecan-2 acts as a suppressor for matrix metalloproteinase-2 (MMP-2) activation, causing suppression of metastasis in the Lewis lung carcinoma 3LL metastatic system [2]. Plus, overexpression of syndecan-2 sensitized human osteosarcoma cells to chemotherapy-induced apoptosis [3]. However, data suggest that syndecan-2 regulates the tumorigenic activities of HT1080 fibrosarcoma cells and that FAK is a key regulator of syndecan-2-mediated tumorigenic activities [4]; plus reduced syndecan-2 expression correlates with reduced tumorigenic activity in colon carcinoma cells [5]

[1] http://www.uniprot.org/uniprot/P34741. [2] Munesue S, J Biol Chem 2007, 282:28164-74. [3] Orosco A, Cancer Res 2007, 67:3708-15. [4] Park H, Cancer Res 2005, 65:9899-905. [5] Kim Y, Oncogene 2003, 22:826-30

Syndecan 3 SDC3, SYND3, N-syndecan Miscellany PHY: May have a role in the organization of cell shape by affecting the actin cytoskeleton, possibly by transferring signals from the cell surface in a sugar-dependent mechanism. Expressed in the nervous system, the adrenal gland, and the spleen [1]

ONC: -


Syndecan 4 SDC4, SYND4, amphiglycan, ryudocan Syntenin PHY: Belongs to the syndecan proteoglycan family along with SDC1, SDC2 and SDC3. Expressed in epithelial and fibroblastic cells

[1] http://www.uniprot.org/uniprot/P31431. [2] Baba F, Breast Cancer Res Treat 2006, 98:91-8. [3] Chalkiadaki G, Int J Biochem Cell Biol

MMMP Biomap #87

[1]

ONC: Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype [2]. Fibroblast growth factor-2 (FGF-2), the most abundant growth factor produced by melanoma cells but not by normal melanocytes, specifically regulates melanoma cell ability to migrate through a syndecan-4-dependent mechanism [3]

2008, Epub ahead of print

TJP1 Tight junction protein 1, ZO-1 (zona occludens 1)

TJP1 TJP2 TJP3

PHY: Tight junction (TJ) formation. Acts as a homodimer or heterodimer with TJP2 and TJP3. Interacts with occludin, claudins, CGN/cingulin

ONC: Reduced expression in breast cancer [1], increased in pancreatic cancer [2]. Decreased expression of adhesion molecules, E-cadherin and ZO-1, in colorectal cancer are closely related to liver metastasis [3]. Cytoplasmic/nuclear relocalization of beta-catenin and ZO-1 from the adherens and tight junctions are common processes of the epithelial-mesenchymal transition (EMT) associated with tumor invasion [4]. Accelerated internalization of junctional membrane proteins (connexin 43, N-cadherin and ZO-1) within endocytic vacuoles is an early event in carcinogenesis induced by DDT (a non-genomic carcinogen) [5]

[1] Hoover KB, Am J Pathol 1998, 153:1767-73. [2] Kleeff J, Pancreas 2001, 23:259-65. [3] Kaihara T, J Exp Clin Cancer Res 2003, 22:117-23. [4] Polette M, Cells Tissues Organs 2007, 185:61-5. [5] Fiorini C, Biochim Biophys Acta 2008, 1778:56-67


TJP1 TJP2

PHY: Tight junction (TJ) formation. Homodimer and heterodimer with ZO1. Interacts with occludin. Defects in TJP2 are involved in familial hypercholanemia (FHCA), a disorder characterized by elevated serum bile acid concentrations, itching and fat malabsorption

ONC: Adenoviral protein Ad9 E4-ORF1 exerts its oncogenic potential at least in part by complexing with candidate tumor suppressor

[1] Glaunsinger BA, EMBO J 2001, 20:5578-86. [2] Fink C, Neoplasia 2006, 8:1019-27

MMMP Biomap #87

protein ZO-2 [1]. Expression of ZO-1 and ZO-2 is reduced (with loss of blood-testis barrier integrity) in testicular carcinoma in situ [2]


TJP1 PHY: Tight junction (TJ) formation. Interacts with occludin, claudins and ZO-1

ONC: -


VCAM1 Vascular cell adhesion molecule 1, CD106

ITG alpha4-beta1 PHY: Regulates leukocyte migration from the blood into tissues during inflammation; expressed on inflamed vascular endothelium, as well as on macrophage-like and dendritic cell types in both normal and inflamed tissue. VCAM-1 expression is stimulated by inflammatory cytokines (e.g. IL-1, TNF) [1]

ONC: Like other cell adhesion molecules, mediates malignant cell extravasation and thus metastasis formation in different tumor models [2], including melanoma [3,4]. Tumor overexpressing VCAM1 may escape immune surveillance [5].

[1] Haverslag R, Cardiovasc Hematol Disord Drug Targets 2008, 8:252-60. [2] Curr Med Chem 2007, 14:377-86. [3] Liang S, Am J Physiol Cell Physiol 2008, 295:C701-7. [4] Klemke M, J Cell Physiol 2007, 212:368-74. [5] Wu TC, Cancer Res 2007, 67:6003-6

Name Aliases Binding partner Physiology / Oncology References

name aliases binding partner physiology / oncology references€¦ · amigo1 or amigo3. may...

Documents