fbw7/cdc4 and endometrial cancer

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FBW7/CDC4 and Endometrial Cancer Michael Mastropole

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FBW7/CDC4 and Endometrial Cancer. Michael Mastropole. Overview. FBW7/CDC4 is a family of genes Tumor suppressor Directly binds to cyclin E Mutated in about 16% of endometrial cancers. Ubiquitylation. http://upload.wikimedia.org/wikipedia/commons/7/7f/Ubiquitylation.png. - PowerPoint PPT Presentation

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Page 1: FBW7/CDC4 and Endometrial Cancer

FBW7/CDC4 and Endometrial Cancer

Michael Mastropole

Page 2: FBW7/CDC4 and Endometrial Cancer

Overview

• FBW7/CDC4 is a family of genes• Tumor suppressor• Directly binds to cyclin E• Mutated in about 16% of endometrial cancers

Page 3: FBW7/CDC4 and Endometrial Cancer

Ubiquitylation

http://upload.wikimedia.org/wikipedia/commons/7/7f/Ubiquitylation.png

Page 4: FBW7/CDC4 and Endometrial Cancer

The SCF Complex (E3 ligase)

Wang et al. 2012

Page 5: FBW7/CDC4 and Endometrial Cancer

CDC4 targets Cyclin E for Proteolysis

Strohmaier et al. 2001

Page 6: FBW7/CDC4 and Endometrial Cancer

http://eweb.furman.edu/~wworthen/bio111/4cyclins.jpg

Cyclin E is required for G1/S Transition

Page 7: FBW7/CDC4 and Endometrial Cancer

Mouse Model

Wang et al. 2012

Page 8: FBW7/CDC4 and Endometrial Cancer

Endometrial Cancer

• Endometrium- lining of the uterus

• Typically occurs within a few decades of menopause

• 49,560 new cases in 2013

Page 9: FBW7/CDC4 and Endometrial Cancer

hCDC4 mutations

Spruck et al. 2002

Page 10: FBW7/CDC4 and Endometrial Cancer

Treatments

• Surgery– Hysterectomy along with removal of ovaries,

fallopian tubes, and lymph nodes– Helps stage the cancer

• Chemotherapy– Taxol

• Radiation• Potential Treatments– Cdk2 inhibitors

www.cancer.org

Page 11: FBW7/CDC4 and Endometrial Cancer

Prognosis

• 1 year survival rate– 92%

• 5 year survival rate if cancer has not spread– 95%

• 5 year survival rate if cancer has spread– 23%

www.nlm.nih.gov

Page 12: FBW7/CDC4 and Endometrial Cancer

References

• http://www.nature.com/nature/journal/v413/n6853/full/413316a0.html

• http://cancerres.aacrjournals.org/content/62/16/4535.long

• http://www.cancer.org/cancer/endometrialcancer/detailedguide/endometrial-uterine-cancer-treating-by-stage

• http://www.nlm.nih.gov/medlineplus/ency/article/000910.htm

• http://www.sciencedirect.com/science/article/pii/S0014579312002049