Prostate cancer is the second most commonly diagnosed cancer in American Men. Prostate cancer that has developed resistance to androgen deprivation therapy, termed Castration-Resistant Prostate Cancer, is a lethal disease. The Polycomb Group Protein EZH2, an enzyme that catalyzes histone H3 lysine 27 trimethylation (H3K27me3), is among the most up-regulated genes in CRPC. How EZH2 regulates prostate cancer progression, however is incompletely understood. In our preliminary studies, mass spec analysis of EZH2 in prostate cancer cells pulled down C10orf12, a protein that has not been previously characterized in prostate cancer. Our preliminary data further showed that C10orf12 mediates EZH2 interaction with G9a, a histone methyltransferase that catalyzes methylation of H3 at lysine 9. Our central hypothesis is that C10orf12 acts as a scaffold protein to recruit EZH2 to G9a targets to repress gene expression and promote prostate cancer progression. The goal of this proposal is to determine how C10orf12 mediates EZH2 and G9a protein interaction, what are the roles of the EZH2-G9a complex in prostate cancer, and how they can be therapeutically targeted using G9a inhibitors.
|Effective start/end date||9/1/17 → 8/31/20|
- U.S. Army Medical Research and Materiel Command (W81XWH-17-1-0578)