The EZH2 and Chromosomal Passenger Complex Network in Prostate Cancer

Each year over 240,000 American men are diagnosed with prostate cancer. Most prostate cancers if detected early can be effectively treated with chemotherapy and/or radiotherapy. Unfortunately, prostate cancer is often diagnosed too late, when tumors have metastasized - spread to other parts of the body. As cancer metastases are often resistant to conventional treatments, the mortality rate for such patients is nearly 100%. As a result, prostate cancer remains the second leading cause of cancer-related deaths in American men. Increased understanding of the molecular events associated with prostate cancer progression is critical to the development of therapeutic approaches to improve the clinical outcome of prostate cancer patients. EZH2, a Polycomb group (PcG) protein and Aurora kinases along with their binding partners, the chromosomal passenger complex (CPC) proteins (Survivin, Borealin, and INCENP) have been shown to be upregulated in prostate cancer and suggested to play an important role in prostate cancer progression. However, the mechanisms responsible for the upregulation of Aurora kinases and CPC proteins in prostate cancer and the potential functional relationship between CPC and PcG proteins in prostate cancer have not been investigated. The proposed studies will dissect the regulatory and functional network among PcG and CPC proteins in prostate cancer and their coordinated role and regulation during prostate cancer progression. Successful completion of this project will provide novel mechanistic insights into prostate cancer progression and provide evidence of the therapeutic potential of combinational targeting of PcG and CPC proteins for metastatic prostate cancer.