Stanley Zhou
Changmeng Cai
Mathieu Lupien
Housheng Hansen He
1 Princess Margaret Cancer Centre, University Health Network, Toronto, Canada;
2 Department of Medical Biophysics, University of Toronto, Toronto, Canada;
3 Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA 02125, USA;
4 Ontario Institute for Cancer Research, Toronto, ON, Canada
Received Date: 2020-07-15
Rev Recd Date:2020-08-18
Abstract
Abstract
Prostate cancer is the most commonly diagnosed noncutaneous cancers in North American men. While androgen deprivation has remained as the cornerstone of prostate cancer treatment, resistance ensues leading to lethal disease. Forkhead box A1 (FOXA1) encodes a pioneer factor that induces open chromatin conformation to allow the binding of other transcription factors. Through direct interactions with the Androgen Receptor (AR), FOXA1 helps to shape AR signaling that drives the growth and survival of normal prostate and prostate cancer cells. FOXA1 also possesses an AR-independent role of regulating epithelial-to-mesenchymal transition (EMT). In prostate cancer, mutations converge onto the coding sequence and cis-regulatory elements (CREs) of FOXA1, leading to functional alterations. In addition, FOXA1 activity in prostate cancer can be modulated post-translationally through various mechanisms such as LSD1-mediated protein demethylation. In this review, we describe the latest discoveries related to the function and regulation of FOXA1 in prostate cancer, pointing to their relevance to guide future clinical interventions.Keywords: FOXA1,
pioneer factor,
transcription factor,
prostate cancer,
epigenetics
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