fbw7/cdc4 and endometrial cancer

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

The SCF Complex (E3 ligase)

Wang et al. 2012

CDC4 targets Cyclin E for Proteolysis

Strohmaier et al. 2001

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

Cyclin E is required for G1/S Transition

Mouse Model

Wang et al. 2012

Endometrial Cancer

• Endometrium- lining of the uterus

• Typically occurs within a few decades of menopause

• 49,560 new cases in 2013

hCDC4 mutations

Spruck et al. 2002

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

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

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