Identification of the Epigenetic Reader CBX2 As a Potential Drug Target in Advanced Prostate Cancer

Overview

Journal Clin Epigenetics

Publisher Biomed Central

Specialty Genetics

Date 2016 Feb 16

PMID 26877821

Citations 45

Authors

Pier-Luc Clermont

Francesco Crea

Yan Ting Chiang

Dong Lin

Amy Zhang

James Z L Wang

Abhijit Parolia

Rebecca Wu

Hui Xue

Yuwei Wang

Jiarui Ding

Kelsie L Thu

Wan L Lam

Sohrab P Shah

Colin C Collins

Yuzhuo Wang

Cheryl D Helgason

Affiliations

Soon will be listed here.

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.

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