Collaboration of kras and androgen receptor signaling stimulates EZH2 expression and tumor-propagating cells in prostate cancer

Houjian Cai, Sanaz Memarzadeh, Tanya Stoyanova, Zanna Beharry, Andrew S. Kraft, Owen N. Witte

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Elevation of the chromatin repression factor enhancer of zeste homolog (EZH2) is associated with progression and poor prognosis in several human cancers including prostate cancer. However, the mechanisms driving EZH2 expression are not fully understood. In this study, we investigated the functional synergy in prostate cancers in mice resulting from activation of the androgen receptor, Kras, and Akt, which drives three of the most frequently activated oncogenic signaling pathways in prostate cancer. Although, any two of these three events were sufficient to promote the formation and progression of prostate cancer, only the synergy of androgen receptor and Kras signaling could elevate EZH2 expression and expand prostate cancer progenitor cells in vivo. Our findings have revealed a genetic mechanism resulting in enhanced EZH2 expression during the progression of aggressive prostate cancer, with important implications for understanding how to target advanced disease where cancer progenitor cells may be critical.

Original languageEnglish (US)
Pages (from-to)4672-4681
Number of pages10
JournalCancer Research
Volume72
Issue number18
DOIs
StatePublished - Sep 15 2012

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Collaboration of kras and androgen receptor signaling stimulates EZH2 expression and tumor-propagating cells in prostate cancer'. Together they form a unique fingerprint.

  • Cite this