Tenascin-X promotes epithelial-to-mesenchymal transition by activating latent TGF-[Beta]

• Published in: The Journal of cell biology Vol. 205; no. 3; p. 409
• Main Authors: Alcaraz, Lindsay B, Exposito, Jean-Yves, Chuvin, Nicolas, Pommier, Roxane M, Cluzel, Caroline, Martel, Sylvie, Sentis, Stéphanie, Bartholin, Laurent, Lethias, Claire, Valcourt, Ulrich
• Format: Journal Article
• Language: English
• Published: New York Rockefeller University Press 12-05-2014
• Subjects: Bioavailability; Cell adhesion & migration; Cellular biology; Glycoproteins; Homeostasis; Matrix; Tissues
• ISSN: 0021-9525; 1540-8140

Transforming growth factor β (TGF-β) isoforms are secreted as inactive complexes formed through noncovalent interactions between the bioactive TGF-β entity and its N-terminal latency-associated peptide prodomain. Extracellular activation of the latent TGF-β complex is a crucial step in the regulation of TGF-β 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-β complex in vitro and in vivo, thus regulating the bioavailability of mature TGF-β 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 α11β1 integrin as a cell surface receptor for TNX and show that this integrin is crucial to elicit FBG-mediated activation of latent TGF-β and subsequent epithelial-to-mesenchymal transition in mammary epithelial cells.