Role of transcriptional corepressor CtBP1 in prostate cancer progression

Rui Wang, Irfan A. Asangani, Balabhadrapatruni V S K Chakravarthi, Bushra Ateeq, Robert J. Lonigro, Qi Cao, Ram Shankar Mani, Daniel F. Camacho, Natalie McGregor, Taibriana E W 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. PientaNallasivam Palanisamy, Lakshmi P. Kunju, Mark A. Rubin, Arul M. Chinnaiyan, Sooryanarayana Varambally

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)905-914
Number of pages10
JournalNeoplasia (United States)
Volume14
Issue number10
DOIs
StatePublished - Oct 2012

ASJC Scopus subject areas

  • Cancer Research

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