TGF-β in developmental and fibrogenic EMTs

TGF-beta plays a prominent role as an inducer of epithelial-mesenchymal transitions (EMTs) during development and wound healing and in disease conditions such as fibrosis and cancer. During these processes EMT occurs together with changes in cell proliferation, differentiation, communication, and extracellular matrix remodeling that are orchestrated by multiple signaling inputs besides TGF-beta. Chief among these inputs is RAS-MAPK signaling, which is frequently required for EMT induction by TGF-beta. Recent work elucidated the molecular basis for the cooperation between the TGF-beta-SMAD and RAS-MAPK pathways in the induction of EMT in em-bryonic, adult and carcinoma epithelial cells. These studies also provided direct mechanistic links between EMT and progenitor cell differentiation during gastrulation or intra-tumoral fibrosis during cancer metastasis. These insights illuminate the nature of TGF-beta driven EMTs as part of broader processes during development, fibro-genesis and metastasis.

Automated summary

TGF-beta plays a crucial role in development, wound healing, fibrosis, and cancer by inducing epithelial-mesenchymal transitions (EMTs). EMTs are regulated by multiple signaling inputs, with RAS-MAPK signaling frequently required for EMT induction by TGF-beta. Recent studies have revealed the molecular basis for the cooperation between the TGF-beta-SMAD and RAS-MAPK pathways in EMT induction, offering insights into EMT and progenitor cell differentiation during gastrulation and cancer metastasis.