STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion
Copyright policy )STAT3 mediates TGF-β1-induced TWIST1 expression and prostate cancer invasion
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.
- Konyang University Korea (Republic of)
Male, STAT3 Transcription Factor, Epithelial-Mesenchymal Transition, Dose-Response Relationship, Drug, Twist-Related Protein 1, Nuclear Proteins, Prostatic Neoplasms, Hypoxia-Inducible Factor 1, alpha Subunit, Gene Expression Regulation, Neoplastic, Transforming Growth Factor beta1, Cell Line, Tumor, Mutation, Disease Progression, Humans, Neoplasm Invasiveness, Gene Silencing, Neoplasm Metastasis, Phosphorylation, Genes, Dominant
Male, STAT3 Transcription Factor, Epithelial-Mesenchymal Transition, Dose-Response Relationship, Drug, Twist-Related Protein 1, Nuclear Proteins, Prostatic Neoplasms, Hypoxia-Inducible Factor 1, alpha Subunit, Gene Expression Regulation, Neoplastic, Transforming Growth Factor beta1, Cell Line, Tumor, Mutation, Disease Progression, Humans, Neoplasm Invasiveness, Gene Silencing, Neoplasm Metastasis, Phosphorylation, Genes, Dominant
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