Title | EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Xu K, Wu ZJeremy, Groner AC, He HHansen, 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, X Liu S, Brown M |
Journal | Science |
Volume | 338 |
Issue | 6113 |
Pagination | 1465-9 |
Date Published | 2012 Dec 14 |
ISSN | 1095-9203 |
Keywords | Animals, Castration, Cell Line, Tumor, Cohort Studies, Enhancer of Zeste Homolog 2 Protein, Gene Expression Regulation, Neoplastic, Gene Silencing, Humans, Jumonji Domain-Containing Histone Demethylases, Male, Methyltransferases, Mice, Mice, Inbred ICR, Mice, SCID, Oncogene Proteins, Polycomb Repressive Complex 2, Prostatic Neoplasms, Protein Structure, Tertiary, Receptors, Androgen, Xenograft Model Antitumor Assays |
Abstract | 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. |
DOI | 10.1126/science.1227604 |
Alternate Journal | Science |
PubMed ID | 23239736 |
Grant List | CA131945 / CA / NCI NIH HHS / United States GM99409 / GM / NIGMS NIH HHS / United States CA111803 / CA / NCI NIH HHS / United States CA090381 / CA / NCI NIH HHS / United States CA85859 / CA / NCI NIH HHS / United States CA097186 / CA / NCI NIH HHS / United States CA89021 / CA / NCI NIH HHS / United States CA166507 / CA / NCI NIH HHS / United States CA90381 / CA / NCI NIH HHS / United States |
Related Faculty:
Massimo Loda, M.D.