EZH2 Oncogenic Activity in Castration-Resistant Prostate Cancer Cells Is Polycomb-Independent Academic Article uri icon


MeSH Major

  • Oncogene Proteins
  • Polycomb Repressive Complex 2
  • Prostatic Neoplasms


  • 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.

publication date

  • December 14, 2012



  • Academic Article



  • eng

PubMed Central ID

  • PMC3625962

Digital Object Identifier (DOI)

  • 10.1126/science.1227604

PubMed ID

  • 23239736

Additional Document Info

start page

  • 1465

end page

  • 9


  • 338


  • 6113