Extracellular Hsp90 as a Novel Epigenetic Regulator of EMT and Metastatic Risk in Prostate Cancer

摘要

In general, the role of eHsp90 in tumor progression has not been well characterized Our work provides novel mechanistic insights into the EMT- promoting activity of eHsp90. Our preliminary findings indicate that eHsp90 is a newly identified regulator of the oncogenic polycomb regulator EZH2. eHsp90 was found to induce EZH2 expression and to direct its recruitment to the promoters of target genes. In this latter capacity, eHsp90 promoted EZH2 s methyltransferase activity, enabling the repression of tumor suppressor genes such as the EMT gatekeeper E-cadherin. Moreover, xenograft studies demonstrate that an eHsp90-EZH2 axis is essential for eHsp90-mediated tumor invasion. Therefore, our findings implicate an eHsp90-EZH2 oncogenic pathway that contributes to early invasive events in prostate cancer.