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

J Cell Biol. 2014 May 12;205(3):409-28. doi: 10.1083/jcb.201308031.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cell Adhesion
  • Cell Line, Tumor
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition*
  • Female
  • HEK293 Cells
  • Humans
  • Integrins / genetics
  • Integrins / metabolism
  • Mammary Glands, Animal / metabolism*
  • Mammary Glands, Human / metabolism*
  • Mice
  • Phosphorylation
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • RNA Interference
  • Receptors, Collagen / genetics
  • Receptors, Collagen / metabolism
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Smad Proteins / genetics
  • Smad Proteins / metabolism
  • Tenascin / genetics
  • Tenascin / metabolism*
  • Transfection
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / metabolism*


  • Integrins
  • Protein Precursors
  • Receptors, Collagen
  • Recombinant Proteins
  • Smad Proteins
  • Tenascin
  • Transforming Growth Factor beta1
  • integrin alpha11beta1
  • tenascin X