Tenascin-X promotes epithelial-to-mesenchymal transition by activating latent TGF-?.

ABSTRACT: Transforming growth factor ? (TGF-?) isoforms are secreted as inactive complexes formed through noncovalent interactions between the bioactive TGF-? entity and its N-terminal latency-associated peptide prodomain. Extracellular activation of the latent TGF-? complex is a crucial step in the regulation of TGF-? function for tissue homeostasis. We show that the fibrinogen-like (FBG) domain of the matrix glycoprotein tenascin-X (TNX) interacts physically with the small latent TGF-? complex in vitro and in vivo, thus regulating the bioavailability of mature TGF-? to cells by activating the latent cytokine into an active molecule. Activation by the FBG domain most likely occurs through a conformational change in the latent complex and involves a novel cell adhesion-dependent mechanism. We identify ?11?1 integrin as a cell surface receptor for TNX and show that this integrin is crucial to elicit FBG-mediated activation of latent TGF-? and subsequent epithelial-to-mesenchymal transition in mammary epithelial cells.

SUBMITTER: Alcaraz LB 

PROVIDER: S-EPMC4018787 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature