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.
EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent / Xu, K.; Wu, Z. J.; Groner, A. C.; He, H. H.; Cai, C.; Lis, R. T.; Wu, X.; Stack, E. C.; Loda, M.; Liu, T.; Xu, H.; Cato, L.; Thornton, J. E.; Gregory, R. I.; Morrissey, C.; Vessella, R. L.; Montironi, Rodolfo; Magi Galluzzi, C.; Kantoff, P. W.; Balk, S. P.; Liu, X. S.; Brown, M.. - In: SCIENCE. - ISSN 0036-8075. - STAMPA. - 338:6113(2012), pp. 1465-1469. [10.1126/science.1227604]
EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent
MONTIRONI, RODOLFO;
2012-01-01
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
