EZH2 Oncogenic Activity in Castration-Resistant Prostate Cancer Cells Is Polycomb-Independent

Academic Article

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.
  • Published In

  • Science  Journal
  • Digital Object Identifier (doi)

    Author List

  • Xu K; Wu ZJ; Groner AC; He HH; Cai C; Lis RT; Wu X; Stack EC; Loda M; Liu T
  • Start Page

  • 1465
  • End Page

  • 1469
  • Volume

  • 338
  • Issue

  • 6113