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

Clermont, Pier-Luc; Crea, Francesco; Chiang, Yan Ting; Lin, Dong; Zhang, Amy; Wang, James Z. L.; Parolia, Abhijit; Wu, Rebecca; Xue, Hui; Wang, Yuwei; Ding, Jiarui; Thu, Kelsie L.; Lam, Wan L.; Shah, Sohrab P.; Collins, Colin C.; Wang, Yuzhuo and Helgason, Cheryl D. (2016). Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer. Clinical Epigenetics, 8(16)

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DOI (Digital Object Identifier) Link: https://doi.org/10.1186/s13148-016-0182-9
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Abstract

Background
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.

Results
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.

Conclusions
Taken together, this study provides the first evidence that CBX2 inhibition induces cancer cell death, positioning CBX2 as an attractive drug target in lethal CRPC.

Item Type: Journal Item
Copyright Holders: 2016 The Authors
ISSN: 1868-7083
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetNot SetMichael Smith Foundation for Health Research
Extra Information: Castration-resistant prostate cancer; CBX2; Epigenetics; Metastatic prostate cancer; Polycomb
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 45760
Depositing User: Francesco Crea
Date Deposited: 22 Mar 2016 16:55
Last Modified: 23 May 2019 07:36
URI: http://oro.open.ac.uk/id/eprint/45760
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