title: Role of transcriptional corepressor CtBP1 in prostate cancer progression.
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.
authors.affiliation: Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Irfan A
authors.initials: IA
authors.lastname: Asangani
authors.forename: Balabhadrapatruni V S K
authors.initials: BV
authors.lastname: Chakravarthi
authors.forename: Bushra
authors.initials: B
authors.lastname: Ateeq
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lonigro
authors.forename: Qi
authors.initials: Q
authors.lastname: Cao
authors.forename: Ram-Shankar
authors.initials: RS
authors.lastname: Mani
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Camacho
authors.forename: Natalie
authors.initials: N
authors.lastname: McGregor
authors.forename: Taibriana E W
authors.initials: TE
authors.lastname: Schumann
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Jing
authors.forename: Radhika
authors.initials: R
authors.lastname: Menawat
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tomlins
authors.forename: Heng
authors.initials: H
authors.lastname: Zheng
authors.forename: Arie P
authors.initials: AP
authors.lastname: Otte
authors.forename: Rohit
authors.initials: R
authors.lastname: Mehra
authors.forename: Javed
authors.initials: J
authors.lastname: Siddiqui
authors.forename: Saravana M
authors.initials: SM
authors.lastname: Dhanasekaran
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Nyati
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Pienta
authors.forename: Nallasivam
authors.initials: N
authors.lastname: Palanisamy
authors.forename: Lakshmi P
authors.initials: LP
authors.lastname: Kunju
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Sooryanarayana
authors.initials: S
authors.lastname: Varambally
mesh_terms: D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002465:Cell Movement; D049109:Cell Proliferation; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000378:metabolism / Q000473:pathology; D047369:Chromatin Immunoprecipitation; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000517:prevention & control / Q000556:secondary*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology* / Q000517:prevention & control; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
chemical_list: D004268:DNA-Binding Proteins; D034741:RNA, Small Interfering; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein