title: Identification of the epigenetic reader CBX2 as a potential drug target in advanced prostate cancer.
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.
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada ; Faculty of Medicine, MD Program, Université Laval, 1050, avenue de la Médecine, Québec, QC G1V 0A6 Canada.
authors.forename: Pier-Luc
authors.initials: PL
authors.lastname: Clermont
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada ; Vancouver Prostate Centre, 899 West 12th Avenue, Vancouver, British Columbia V5Z 1M9 Canada ; Department of Life, Health, and Chemical Sciences, The Open University, Milton Keynes, MK7 6BH UK.
authors.forename: Francesco
authors.initials: F
authors.lastname: Crea
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada ; Vancouver Prostate Centre, 899 West 12th Avenue, Vancouver, British Columbia V5Z 1M9 Canada.
authors.forename: Yan Ting
authors.initials: YT
authors.lastname: Chiang
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada ; Vancouver Prostate Centre, 899 West 12th Avenue, Vancouver, British Columbia V5Z 1M9 Canada.
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: Amy
authors.initials: A
authors.lastname: Zhang
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: James Z L
authors.initials: JZ
authors.lastname: Wang
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: Abhijit
authors.initials: A
authors.lastname: Parolia
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Computer Science, Faculty of Science, University of British Columbia, 2366 Main Mall, Vancouver, British Columbia V6T 1Z4 Canada ; Department of Molecular Oncology, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: Jiarui
authors.initials: J
authors.lastname: Ding
authors.affiliation: Genetics Unit, Department of Integrative Oncology, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: Kelsie L
authors.initials: KL
authors.lastname: Thu
authors.affiliation: Genetics Unit, Department of Integrative Oncology, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
authors.affiliation: Department of Computer Science, Faculty of Science, University of British Columbia, 2366 Main Mall, Vancouver, British Columbia V6T 1Z4 Canada ; Department of Molecular Oncology, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada.
authors.forename: Sohrab P
authors.initials: SP
authors.lastname: Shah
authors.affiliation: Vancouver Prostate Centre, 899 West 12th Avenue, Vancouver, British Columbia V5Z 1M9 Canada ; Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, British Columbia V5Z 1M9 Canada.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Collins
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada ; Vancouver Prostate Centre, 899 West 12th Avenue, Vancouver, British Columbia V5Z 1M9 Canada ; Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, British Columbia V5Z 1M9 Canada.
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Experimental Therapeutics, British Columbia Cancer Research Centre, 675 W 10th Avenue, Vancouver, British Columbia V5Z 1L3 Canada ; Department of Surgery, University of British Columbia, 910 W 10th Avenue, Vancouver, British Columbia V5Z 4E3 Canada.
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Helgason
mesh_terms: D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D044127:Epigenesis, Genetic / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D063150:Polycomb Repressive Complex 1 / Q000187:drug effects* / Q000502:physiology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy / Q000235:genetics; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: C570479:CBX2 protein, human; D063150:Polycomb Repressive Complex 1; D053148:Caspase 3
keywords: CBX2; Castration-resistant prostate cancer; Epigenetics; Metastatic prostate cancer; Polycomb