EZH2 oncogenic activity in castration-resistant prostate cancer cells is Polycomb-independent

K Xu, ZJ Wu, AC Groner, HH He, C Cai, RT Lis, X Wu… - Science, 2012 - science.org
K Xu, ZJ Wu, AC Groner, HH He, C Cai, RT Lis, X Wu, EC Stack, M Loda, T Liu, H Xu, L Cato…
Science, 2012science.org
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 …
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.
AAAS