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Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer

Lin, Dong; Dong, Xin; Wang, Kendric; Wyatt, Alexander W.; Crea, Francesco; Xue, Hui; Wang, Yuwei; Wu, Rebecca; Bell, Robert H.; Haegert, Anne; Brahmbhatt, Sonal; Hurtado-Coll, Antonio; Gout, Peter W.; Fazli, Ladan; Gleave, Martin E.; Collins, Colin C. and Wang, Yuzhuo (2015). Identification of DEK as a potential therapeutic target for neuroendocrine prostate cancer. Oncotarget, 6(3) pp. 1806–1820.

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DOI (Digital Object Identifier) Link: https://doi.org/10.18632/oncotarget.2809
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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.

Item Type: Journal Item
Copyright Holders: 2014 Impact Journals
ISSN: 1949-2553
Keywords: neuroendocrine prostate cancer; patient-derived xenograft model; DEK; biomarker
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: 45784
Depositing User: Francesco Crea
Date Deposited: 24 Mar 2016 10:45
Last Modified: 08 Dec 2018 08:19
URI: http://oro.open.ac.uk/id/eprint/45784
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