title: Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer.
abstract: Neuroendocrine prostate cancer (NEPC) is an aggressive subtype of prostate cancer which does not respond to hormone therapy. Research of NEPC has been hampered by a lack of clinically relevant in vivo models. Recently, we developed a first-in-field patient tissue-derived xenograft model of complete neuroendocrine transdifferentiation of prostate adenocarcinoma. By comparing gene expression profiles of a transplantable adenocarcinoma line (LTL331) and its NEPC subline (LTL331R), we identified DEK as a potential biomarker and therapeutic target for NEPC. In the present study, elevated DEK protein expression was observed in all NEPC xenograft models and clinical NEPC cases, as opposed to their benign counterparts (0%), hormonal naïve prostate cancer (2.45%) and castration-resistant prostate cancer (29.55%). Elevated DEK expression was found to be an independent clinical risk factor, associated with shorter disease-free survival of hormonal naïve prostate cancer patients. DEK silencing in PC-3 cells led to a marked reduction in cell proliferation, cell migration and invasion. The results suggest that DEK plays an important role in the progression of prostate cancer, especially to NEPC, and provides a potential biomarker to aid risk stratification of prostate cancer and a novel target for therapy of NEPC.
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Dong
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Kendric
authors.initials: K
authors.lastname: Wang
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Wyatt
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.|Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Francesco
authors.initials: F
authors.lastname: Crea
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Hui
authors.initials: H
authors.lastname: Xue
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wu
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bell
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Haegert
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Sonal
authors.initials: S
authors.lastname: Brahmbhatt
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Antonio
authors.initials: A
authors.lastname: Hurtado-Coll
authors.affiliation: Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gout
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Ladan
authors.initials: L
authors.lastname: Fazli
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
authors.forename: Colin C
authors.initials: CC
authors.lastname: Collins
authors.affiliation: Vancouver Prostate Centre & Department of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.|Department of Experimental Therapeutics, BC Cancer Agency, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Yuzhuo
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism* / Q000473:pathology; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis* / Q000235:genetics; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; D015513:Oncogene Proteins; D000075223:Poly-ADP-Ribose Binding Proteins