Slug, a unique Androgen-regulated transcription factor, coordinates androgen receptor to facilitate castration resistance in prostate cancer

Kaijie Wu, Crystal Gore, Lin Yang, Ladan Fazli, Martin Gleave, Rey Chen Pong, Guanghua Xiao, Linlin Zhang, Eun Jin Yun, Shu Fen Tseng, Payal Kapur, Dalin He, Jer Tsong Hsieh

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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 andARnot only in transcriptional regulation but also in protein bioactivity, and Slug-AR complex plays an important role in accelerating the androgenindependent outgrowth of CRPC.

Original languageEnglish (US)
Pages (from-to)1496-1507
Number of pages12
JournalMolecular Endocrinology
Volume26
Issue number9
DOIs
StatePublished - Sep 2012

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Gastropoda
Castration
Androgen Receptors
Androgens
Prostatic Neoplasms
Transcription Factors
Zinc Fingers
Snails
Growth
Genes
Neoplasms
Proteins
Neoplasm Metastasis
Ligands
Phenotype
Mutation

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Slug, a unique Androgen-regulated transcription factor, coordinates androgen receptor to facilitate castration resistance in prostate cancer. / Wu, Kaijie; Gore, Crystal; Yang, Lin; Fazli, Ladan; Gleave, Martin; Pong, Rey Chen; Xiao, Guanghua; Zhang, Linlin; Yun, Eun Jin; Tseng, Shu Fen; Kapur, Payal; He, Dalin; Hsieh, Jer Tsong.

In: Molecular Endocrinology, Vol. 26, No. 9, 09.2012, p. 1496-1507.

Research output: Contribution to journalArticle

Wu, Kaijie ; Gore, Crystal ; Yang, Lin ; Fazli, Ladan ; Gleave, Martin ; Pong, Rey Chen ; Xiao, Guanghua ; Zhang, Linlin ; Yun, Eun Jin ; Tseng, Shu Fen ; Kapur, Payal ; He, Dalin ; Hsieh, Jer Tsong. / Slug, a unique Androgen-regulated transcription factor, coordinates androgen receptor to facilitate castration resistance in prostate cancer. In: Molecular Endocrinology. 2012 ; Vol. 26, No. 9. pp. 1496-1507.
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