title: Slug, a unique androgen-regulated transcription factor, coordinates androgen receptor to facilitate castration resistance in prostate cancer.
abstract: Prostate cancer (PCa) becomes lethal when cancer cells develop into castration-resistant PCa (CRPC). Androgen receptor (AR) gene mutation, altered AR regulation, or overexpression of AR often found in CRPC is believed to become one of the key factors to the lethal phenotype. Here we identify Slug, a member of the Snail family of zinc-finger transcription factors associated with cancer metastasis, as a unique androgen-responsive gene in PCa cells. In addition, the presence of constitutively active AR can induce Slug expression in a ligand-independent manner. Slug overexpression will increase AR protein expression and form a complex with AR. In addition, Slug appears to be a novel coactivator to enhance AR transcriptional activities and AR-mediated cell growth with or without androgen. In vivo, elevated Slug expression provides a growth advantage for PCa cells in androgen-deprived conditions. Most importantly, these observations were validated by several data sets from tissue microarrays. Overall, there is a reciprocal regulation between Slug and AR not only in transcriptional regulation but also in protein bioactivity, and Slug-AR complex plays an important role in accelerating the androgen-independent outgrowth of CRPC.
authors: Department of Urology, The First Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an 710061, China.
authors: Kaijie
authors: K
authors: Wu
authors: Crystal
authors: C
authors: Gore
authors: Lin
authors: L
authors: Yang
authors: Ladan
authors: L
authors: Fazli
authors: Martin
authors: M
authors: Gleave
authors: Rey-Chen
authors: RC
authors: Pong
authors: Guanghua
authors: G
authors: Xiao
authors: Linlin
authors: L
authors: Zhang
authors: Eun-Jin
authors: EJ
authors: Yun
authors: Shu-Fen
authors: SF
authors: Tseng
authors: Payal
authors: P
authors: Kapur
authors: Dalin
authors: D
authors: He
authors: Jer-Tsong
authors: JT
authors: Hsieh
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D011944:Receptors, Androgen; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors