Pioneer of prostate cancer: past, present and the future of FOXA1.
10.1007/s13238-020-00786-8
- Author:
Mona TENG
1
;
Stanley ZHOU
1
;
Changmeng CAI
2
;
Mathieu LUPIEN
3
;
Housheng Hansen HE
4
Author Information
1. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada.
2. Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, MA, 02125, USA.
3. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. mathieu.lupien@uhnresearch.ca.
4. Princess Margaret Cancer Centre, University Health Network, Toronto, Canada. hansenhe@uhnresearch.ca.
- Publication Type:Review
- Keywords:
FOXA1;
epigenetics;
pioneer factor;
prostate cancer;
transcription factor
- MeSH:
Amino Acid Sequence;
Epigenesis, Genetic;
Epithelial-Mesenchymal Transition;
Gene Expression Regulation, Neoplastic;
Hepatocyte Nuclear Factor 3-alpha/metabolism*;
Histone Demethylases/metabolism*;
Histones/metabolism*;
Humans;
Male;
Mutation;
Prostate/pathology*;
Prostatic Neoplasms/pathology*;
Protein Binding;
Protein Processing, Post-Translational;
Receptors, Androgen/metabolism*;
Signal Transduction;
Transcription, Genetic
- From:
Protein & Cell
2021;12(1):29-38
- CountryChina
- Language:English
-
Abstract:
Prostate cancer is the most commonly diagnosed non-cutaneous 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.
