Modulation of androgen receptor by FOXA1 and FOXO1 factors in prostate cancer

Yu Zhao, Donald J. Tindall, Haojie Huang

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Androgens and the androgen receptor (AR) are essential for growth and differentiation of the normal prostate gland as well as proliferation and survival of prostate cancer (PCa). Increasing evidence suggests that reactivation of the AR plays a pivotal role in disease progression to castration- resistant PCa (CRPC). Forkhead box (FOX) factors exert two distinct effects on AR function in PCa. The A-class of FOX proteins, especially FOXA1, functions as a pioneer factor to facilitate AR transactivation and PCa growth. In contrast, the O-class of FOX proteins such as FOXO1 and FOXO3, which are downstream effectors of the PTEN tumor suppressor, inhibit the transcriptional activity of either full-length AR or constitutively active splice variants of AR in a direct or indirect manner in PCa. FOXO1 also contributes to taxane-mediated inhibition of the AR and CRPC growth. Therefore, FOX family members not only have a tight relationship with AR, but also represent a pivotal group of proteins to be targeted for PCa therapy. The present review focuses primarily on recent advances in the epigenetic, mechanistic and clinical relevant aspects of regulation of the AR by FOXA1 and FOXO1 factors in PCa.

Original languageEnglish (US)
Pages (from-to)614-619
Number of pages6
JournalInternational Journal of Biological Sciences
Volume10
Issue number6
DOIs
StatePublished - Jun 5 2014

Keywords

  • Androgen receptor
  • Androgens
  • FOXA1
  • Prostate cancer

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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