Molecular View of Cancer

Lecture 3:

How do cancer cells move?

How do errors occur in cancer cells?

How do cancer cells invade healthy tissue and metastasize?

Cells “let go” and migrateCells must lose intercellular adhesion and acquire migratory ability

http://www.youtube.com/watch?v=rrMq8uA_6iA

Different cancers tend to form metastases at particular secondary sites 1° tumor

(melanoma)

2° tumor in brain(melanoma)

How do errors occur in cancer cells?

Cancer Tends to Involve Multiple Mutations

Malignant cells invade neighboring tissues, enter blood vessels, and metastasize to different sites

More mutations, more genetic instability, metastatic disease

Proto-oncogenes mutate to oncogenes

Mutations inactivate DNA repair genes

Cells proliferate

Mutation inactivates suppressor gene

Benign tumor cells grow only locally and cannot spread by invasion or metastasis

Time

Multiple pathways to cancer

Other factors influence tumorigenesis

Viral infection and cancer

Virus Associated cancer(s)

Epstein-Barr virus (EBV, “mono”) Burkitt’s lymphoma, nasopharyngeal carcinoma

Hepatitis B and C Liver cancer

Herpes virus-8 Kaposi sarcoma

Human T lymphotrophic virus type 1 (HTLV-I)

T-cell leukemia

Human papilloma virus (HPV) Cervical, genital and oral cancers

Viruses can promote cancer via chronic inflammation or by preventing apoptosis

Other factors influence tumorigenesis

DNA is continually damaged

DNA Repair Genes

Cancer

No cancer

No DNA repair

Normal DNA repair

Base pair mismatch

T CATC

A GTCG

T CAGC

A GTCG

A GTG A GTAG

T CATCT CATC

Heritable cancer syndromes/predisposition

• A mutation in genes involved in DNA repair can lead to cancer syndromes

• DNA repair genes are tumor suppressors

Heritable cancer syndromes/predisposition

• Xeroderma pigmentosum (XP)

• Hereditary breast cancer

• Hereditary non-polyposis colorectal cancer (HNPCC)

Cancer cells show genome instability

• Chromosome rearrangements, changes in copy number, and mutations can both facilitate carcinogenesis and be a result of it

p53 is one of the most important tumor suppressors we have

• Needed for successful DNA repair

• Can halt cell division• Can induce cell death if

cell too damaged

p53 is one of the most important tumor suppressors we have

p53 and cervical cancer

E7 blocks Rb!

Li-Fraumeni Syndrome: a severe cancer syndrome

Next time: Epigenetics and cancer, and cancer therapies