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.
Mesh Terms:
Cell Line, Tumor, Disease Progression, Dose-Response Relationship, Drug, Epithelial-Mesenchymal Transition, Gene Expression Regulation, Neoplastic, Gene Silencing, Genes, Dominant, Humans, Hypoxia-Inducible Factor 1, alpha Subunit, Male, Mutation, Neoplasm Invasiveness, Neoplasm Metastasis, Nuclear Proteins, Phosphorylation, Prostatic Neoplasms, STAT3 Transcription Factor, Transforming Growth Factor beta1, Twist-Related Protein 1
Cancer Lett.
Date: Aug. 09, 2013
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