Transforming growth factor-beta employs HMGA2 to elicit epithelial-mesenchymal transition.

ABSTRACT: Epithelial-mesenchymal transition (EMT) occurs during embryogenesis, carcinoma invasiveness, and metastasis and can be elicited by transforming growth factor-beta (TGF-beta) signaling via intracellular Smad transducers. The molecular mechanisms that control the onset of EMT remain largely unexplored. Transcriptomic analysis revealed that the high mobility group A2 (HMGA2) gene is induced by the Smad pathway during EMT. Endogenous HMGA2 mediates EMT by TGF-beta, whereas ectopic HMGA2 causes irreversible EMT characterized by severe E-cadherin suppression. HMGA2 provides transcriptional input for the expression control of four known regulators of EMT, the zinc-finger proteins Snail and Slug, the basic helix-loop-helix protein Twist, and inhibitor of differentiation 2. We delineate a pathway t

SUBMITTER: Thuault S 

PROVIDER: S-EPMC2064178 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature