TGFβ Signaling in Tumor Initiation, Epithelial-to-Mesenchymal Transition, and Metastasis

Figure 1

Smad-dependent and independent TGFβ pathways. Active TGFβ ligands initiate signaling by binding to TGFβRIs and TGFβRIIs. TGFβ receptors exhibit kinase activities that are necessary for transducing canonical TGFβ signaling by phosphorylating Smads2/3. Activated R-Smads can form a heterotrimeric complex with Smad4 which associates with other cofactors in the nucleus to regulate the expression of TGFβ target genes. Furthermore, downstream signaling can also be transduced via auxiliary pathways such as various brunches of the Mek/Erk, the Rho-like GTPases, and the PI3K/Akt and the p38/MAPK pathways to modulate biological responses including epithelial-to-mesenchymal transition, cell adhesion, migration, and survival.