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.