Cell size and invasion in TGF-beta-induced epithelial to mesenchymal transition is regulated by activation of the mTOR pathway.

ABSTRACT: Epithelial to mesenchymal transition (EMT) occurs during development and cancer progression to metastasis and results in enhanced cell motility and invasion. Transforming growth factor-beta (TGF-beta) induces EMT through Smads, leading to transcriptional regulation, and through non-Smad pathways. We observe that TGF-beta induces increased cell size and protein content during EMT. This translational regulation results from activation by TGF-beta of mammalian target of rapamycin (mTOR) through phosphatidylinositol 3-kinase and Akt, leading to the phosphorylation of S6 kinase 1 and eukaryotic initiation factor 4E-binding protein 1, which are direct regulators of translation initiation. Rapamycin, a specific inhibitor of mTOR complex 1, inhibits the TGF-beta-induced translation pathway and inc

SUBMITTER: Lamouille S 

PROVIDER: S-EPMC2064840 | biostudies-literature | 2007 Jul

REPOSITORIES: biostudies-literature