title: STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion.
abstract: TGF-β1 induces epithelial-mesenchymal transition (EMT) to stimulate cancer cell progression, and TWIST1 is a critical regulator of EMT. In the present study, we determined the underlying mechanisms of TGF-β1-induced TWIST1 expression and its effect on prostate cancer cell invasion. TGF-β1 stimulated STAT3 phosphorylation and HIF-1α expression. Silencing either STAT3 or HIF-1α efficiently attenuated TGF-β1-induced TWIST1 expression. Further ectopic expression of a dominant negative mutant of STAT3 reduced TGF-β1-induced TWIST1 expression. In addition, STAT3 and HIF-1α up-regulated TWIST1 expression by direct binding to a TWIST1 promoter. Strikingly, STAT3 also enhanced TGF-β1-induced TWIST1 expression through HIF-1α stabilization. Collectively, we demonstrate a mechanistic cascade of TGF-β1 up-regulating STAT3 activation and HIF-1α stabilization and subsequent TWIST1 expression, leading to prostate cancer invasion.
authors.affiliation: Department of Pharmacology, Myunggok Medical Research Institute, College of Medicine, Konyang University, Daejeon, Republic of Korea.
authors.forename: Kyung Hwa
authors.initials: KH
authors.lastname: Cho
authors.forename: Kang Jin
authors.initials: KJ
authors.lastname: Jeong
authors.forename: Shang Cheul
authors.initials: SC
authors.lastname: Shin
authors.forename: Jaeku
authors.initials: J
authors.lastname: Kang
authors.forename: Chang Gyo
authors.initials: CG
authors.lastname: Park
authors.forename: Hoi Young
authors.initials: HY
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005799:Genes, Dominant; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D009154:Mutation; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D051879:Twist-Related Protein 1 / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C103173:TWIST1 protein, human; D053773:Transforming Growth Factor beta1; D051879:Twist-Related Protein 1