Epigenetic regulators represent a promising new class of therapeutic targets for cancer.
Enhancer of zeste homolog 2 (EZH2), a subunit of Polycomb repressive complex 2 (PRC2), silences gene expression via its histone methyltransferase activity. We found that the oncogenic function of EZH2 in cells of castration-resistant prostate cancer is independent of its role as a transcriptional repressor. Instead, it involves the ability of EZH2 to act as a coactivator for critical transcription factors including the androgen receptor. This functional switch is dependent on phosphorylation of EZH2 and requires an intact methyltransferase domain. Hence, targeting the non-PRC2 function of EZH2 may have therapeutic efficacy for treating metastatic, hormone-refractory prostate cancer.
Written by:
Xu K, Wu ZJ, Groner AC, He HH, Cai C, Lis RT, Wu X, Stack EC, Loda M, Liu T, Xu H, Cato L, Thornton JE, Gregory RI, Morrissey C, Vessella RL, Montironi R, Magi-Galluzzi C, Kantoff PW, Balk SP, Liu XS, Brown M. Are you the author?
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Reference: Science. 2012 Dec 14;338(6113):1465-9
doi: 10.1126/science.1227604
http://www.ncbi.nlm.nih.gov/pubmed/23239736
PubMed Abstract
PMID: 23239736
