Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer

Clinical Epigenetics
Pier-Luc ClermontCheryl D Helgason

Abstract

While localized prostate cancer (PCa) can be effectively cured, metastatic disease inevitably progresses to a lethal state called castration-resistant prostate cancer (CRPC). Emerging evidence suggests that aberrant epigenetic repression by the polycomb group (PcG) complexes fuels PCa progression, providing novel therapeutic opportunities. In the search for potential epigenetic drivers of CRPC, we analyzed the molecular profile of PcG members in patient-derived xenografts and clinical samples. Overall, our results identify the PcG protein and methyl-lysine reader CBX2 as a potential therapeutic target in advanced PCa. We report that CBX2 was recurrently up-regulated in metastatic CRPC and that elevated CBX2 expression was correlated with poor clinical outcome in PCa cohorts. Furthermore, CBX2 depletion abrogated cell viability and induced caspase 3-mediated apoptosis in metastatic PCa cell lines. Mechanistically explaining this phenotype, microarray analysis in CBX2-depleted cells revealed that CBX2 controls the expression of many key regulators of cell proliferation and metastasis. Taken together, this study provides the first evidence that CBX2 inhibition induces cancer cell death, positioning CBX2 as an attractive drug targe...Continue Reading

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Citations

Aug 10, 2016·Molecular Diagnosis & Therapy·Javier C AnguloSantiago Ropero
Aug 17, 2016·Epigenomics·Joanna D Holbrook
Jun 11, 2019·Expert Opinion on Therapeutic Targets·Maïka JangalMichael Witcher
Sep 2, 2020·The Journal of Cell Biology·Claudia BaumannRabindranath De La Fuente
Apr 25, 2018·Proceedings of the National Academy of Sciences of the United States of America·John K LeeOwen N Witte
Jun 19, 2019·BioMed Research International·Chao TanShengkui Tan
Oct 11, 2017·Journal of Biochemistry·Takayuki KawaguchiJun-Ichi Nakayama
Jun 13, 2021·Scientific Reports·Mengya HeRongguang Zhang
Oct 29, 2021·Technology in Cancer Research & Treatment·Le WangYang Nan

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Datasets Mentioned

BETA
GSE41193

Methods Mentioned

BETA
ubiquitination
xenograft
biopsies
xenografts
biopsy
protein assay

Software Mentioned

R
Oncomine
Ingenuity Pathway Analysis ( IPA )
cBIO
IPA
GraphPad Prism

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