BRD4 regulates key transcription factors that drive epithelial-mesenchymal transition in castration-resistant prostate cancer.

Prostate Cancer and Prostatic Diseases
Jordan S ShafranGerald V Denis

Abstract

Androgen deprivation therapies for the hormone-dependent stages of prostate cancer have become so effective that new forms of chemoresistant tumors are emerging in clinical practice, and require new targeted therapies in the metastatic setting. Yet there are important gaps in our understanding of the relevant transcriptional networks driving this process. Progression from localized to metastatic castration resistant prostate cancer (mCRPC) occurs as a result of accumulated resistance mechanisms that develop upon sustained androgen receptor (AR) suppression. Critical to this progression is the plastic nature by which prostate tumor cells transition from epithelial to mesenchymal states (EMT). Here, using prostate cancer cell lines with different AR composition, we systematically manipulated somatic proteins of the Bromodomain and ExtraTerminal (BET) family (BRD2, BRD3, and BRD4) to determine which BET proteins influence EMT. We used the TCGA repository to correlate the expression of individual BET genes with key EMT genes and determined biochemical recurrence in 414 patients and progression free survival in 488 patients. We found that only BRD4-and not BRD2 or BRD3-regulates the expression of SNAI1 and SNAI2, and that the downre...Continue Reading

References

Oct 19, 2005·Neoplasia : an International Journal for Oncology Research·Steven R SchwarzeDavid F Jarrard
Dec 7, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Karsten GravdalLars A Akslen
Sep 28, 2010·Nature·Panagis FilippakopoulosJames E Bradner
Jan 12, 2011·Nature Biotechnology·James T RobinsonJill P Mesirov
Sep 6, 2011·Cell·Jake E DelmoreConstantine S Mitsiades
Sep 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jennifer A MertzRobert J Sims
Jun 23, 2012·Nature Reviews. Cancer·Anna C Belkina, Gerald V Denis
Sep 6, 2012·Development·Jormay Lim, Jean Paul Thiery
Oct 19, 2012·Cell Adhesion & Migration·Bethany N Smith, Valerie A Odero-Marah
Feb 20, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anna C BelkinaGerald V Denis
Sep 30, 2014·Trends in Molecular Medicine·Rajdeep DasLuke A Selth
Jun 3, 2015·ACS Chemical Biology·Michael ZengerleAlessio Ciulli
Jun 9, 2016·Proceedings of the National Academy of Sciences of the United States of America·Kanak RainaKevin G Coleman
Nov 5, 2016·Cancer Research·Guillaume AndrieuGerald V Denis
Oct 23, 2016·Drug Discovery Today. Technologies·Guillaume AndrieuGerald V Denis
Jan 1, 2015·Asian Journal of Urology·Zheng Cao, Natasha Kyprianou
Feb 14, 2018·Molecular Cancer Research : MCR·Guillaume P Andrieu, Gerald V Denis
Mar 21, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jonathan WeltiUNKNOWN International SU2C/PCF Prostate Cancer Dream Team
Jul 10, 2018·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rahul AggarwalEric J Small
Sep 21, 2018·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Himisha BeltranScott T Tagawa
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal
May 8, 2019·Proceedings of the National Academy of Sciences of the United States of America·Wassim AbidaCharles L Sawyers
May 22, 2019·Molecular Cancer Research : MCR·Jordan S ShafranGerald V Denis

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Mar 26, 2021·Journal of Medicinal Chemistry·Junping PeiLiang Ouyang
Apr 15, 2021·Molecular Therapy Oncolytics·Hua YangHua You
Sep 15, 2021·Stem Cells·Anusree DeyHari Sharan Misra

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