Exaggerated pharmacology versus true toxicity—Part 2

Epithelial cells repress epithelial characteristics and elaborate mesenchymal characteristics to migrate to other locations and acquire new properties. Epithelial plasticity responses are directed through cooperation of signaling pathways, with TGF-β and TGF-β-related proteins playing prominent instructive roles. Epithelial-mesenchymal transitions (EMTs) directed by activin-like molecules, bone morphogenetic proteins, or TGF-β regulate metazoan development and wound healing and drive fibrosis and cancer progression. In carcinomas, diverse EMTs enable stem cell generation, anti-cancer drug resistance, genomic instability, and localized immunosuppression. This review discusses roles of TGF-β and TGF-β-related proteins, and underlying molecular mechanisms, in epithelial plasticity in development and wound healing, fibrosis, and cancer.