Role of Transcriptional Corepressor CtBP1 in Prostate Cancer Progression

Transcriptional repressors and corepressors play a critical role in cellular homeostasis and are frequently altered in cancer. C-terminal binding protein 1 (CtBP1), a transcriptional corepressor that regulates the expression of tumor suppressors and genes involved in cell death, is known to play a...

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Main Authors: Rui Wang, Irfan A Asangani, Balabhadrapatruni VSK Chakravarthi, Bushra Ateeq, Robert J Lonigro, Qi Cao, Mani Ram-Shankar, Daniel F Camacho, Natalie McGregor, Taibriana EW Schumann, Xiaojun Jing, Radhika Menawat, Scott A Tomlins, Heng Zheng, Arie P Otte, Rohit Mehra, Javed Siddiqui, Saravana M Dhanasekaran, Mukesh K Nyati, Kenneth J Pienta, Nallasivam Palanisamy, Lakshmi P Kunju, Mark A Rubin, Arul M Chinnaiyan, Sooryanarayana Varambally
Format: Article
Language:English
Published: Elsevier 2012-10-01
Series:Neoplasia: An International Journal for Oncology Research
Online Access:http://www.sciencedirect.com/science/article/pii/S1476558612800224
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Summary:Transcriptional repressors and corepressors play a critical role in cellular homeostasis and are frequently altered in cancer. C-terminal binding protein 1 (CtBP1), a transcriptional corepressor that regulates the expression of tumor suppressors and genes involved in cell death, is known to play a role in multiple cancers. In this study, we observed the overexpression and mislocalization of CtBP1 in metastatic prostate cancer and demonstrated the functional significance of CtBP1 in prostate cancer progression. Transient and stable knockdown of CtBP1 in prostate cancer cells inhibited their proliferation and invasion. Expression profiling studies of prostate cancer cell lines revealed that multiple tumor suppressor genes are repressed by CtBP1. Furthermore, our studies indicate a role for CtBP1 in conferring radiation resistance to prostate cancer cell lines. In vivo studies using chicken chorioallantoic membrane assay, xenograft studies, and murine metastasis models suggested a role for CtBP1 in prostate tumor growth and metastasis. Taken together, our studies demonstrated that dysregulated expression of CtBP1 plays an important role in prostate cancer progression and may serve as a viable therapeutic target.
ISSN:1476-5586