FOXA1 (also known as hepatocyte nuclear factor 3α, or HNF-3α) is a protein of the FKHD family transcription factors. FOXA1 has been termed as a pioneer transcription factor due to its unique ability of chromatin remodeling in which the chromatin can be decompacted to allow genomic access by nuclear hormone receptors, including androgen receptor (AR) and estrogen receptor (ER). In this review, we discuss our current understanding of FOXA1 regulation of prostatic and non-prostatic AR-chromatin targeting. We present an updated model wherein FOXA1:AR equilibrium in the nuclei defines prostatic AR binding profile, which is perturbed in prostate cancer with FOXA1 and/or AR de-regulation. Finally, we discuss recent efforts in exploring new horizons of AR-independent functions of FOXA1 in prostate cancer and interesting directions to pursue in future studies.
Keywords: Androgen receptor; Chromatin accessibility; EMT; FOXA1; Pioneering factor; Prostate cancer.