Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that 
induces growth arrest, tissue fibrosis, and epithelial-mesenchymal transition 
(EMT) through activation of Smad and non-Smad signaling pathways. EMT is the 
differentiation switch by which polarized epithelial cells differentiate into 
contractile and motile mesenchymal cells. Cell motility and invasive capacity 
are activated upon EMT. Multiple transcription factors, including deltaEF1/ZEB1, 
SIP1/ZEB2, and Snail/SNAI1, are induced by TGF-beta-Smad signaling and play 
critical roles in TGF-beta-induced EMT. In addition, both non-Smad signaling 
activated by TGF-beta and cross-talk with other signaling pathways play 
important roles in induction of EMT. Of these, Ras signaling synergizes with 
TGF-beta-Smad signaling, and plays an important role in the induction of EMT. 
TGF-beta inhibitors prevent invasion and metastasis of advanced cancer through 
multiple mechanisms, including inhibition of EMT. The discovery of molecules 
that inhibit TGF-beta-induced EMT but not TGF-beta-induced growth arrest may be 
an ideal strategy for treatment of invasion and metastasis of cancer.