TGF-β and Smad Signaling in Transcriptome Reprogramming During EMT

Epithelial-mesenchymal transition (EMT) is a differentiation switch between two major cell types, polarized immobile epithelial and contractile and motile mesenchymal/fibroblastic cells. EMT is critical for proper embryonic development and is also relevant to vascular remodeling processes during which endothelial cells generate myoepithelial cells. Similar to all other developmentally relevant differentiation processes, EMT is governed by the concerted action of extracellular polypeptide/morphogenetic factors, transforming growth factor-β (TGF-β) representing one of them. Because of the relevance the EMT process has for tumor cell invasiveness, metastasis, and tissue fibrosis, considerable research effort has recently focused on the mechanism by which TGF-β elicits EMT of normal epithelial and carcinoma cells. Here, we summarize the state of the art with respect to signaling mechanisms and critical effectors of EMT downstream of TGF-β. We also discuss our recent work on this topic and present a wider perspective for the future of this thriving field.