Alcaraz et al. describe how the extracellular matrix protein tenascin-X (TNX) controls cell plasticity by activating the TGF-β signaling pathway.
In addition to their structural and mechanical roles, extracellular matrix proteins often have signaling functions that influence cell fate choices. Type I collagen, for example, induces epithelial-to-mesenchymal transitions (EMTs) by regulating several cell-signaling pathways. The matrix protein TNX binds to multiple collagens and helps assemble them into functional three-dimensional networks, but whether TNX also has signaling functions is unknown.
Alcaraz et al. found that breast epithelial cells quickly switched to a mesenchymal fate when plated onto coverslips coated with the fibrinogen-like (FBG) domain of TNX. This transition depended on the TGF-β signaling pathway. TGF-β is secreted in an inactive complex, in which the mature cytokine is masked by an inhibitory peptide. The FBG domain of TNX bound and activated the latent TGF-β complex, probably by inducing a conformational change that exposes the cytokine to its cell surface receptor.
Alcaraz et al. identified the integrin α11β1 as the adhesion receptor that binds to the FBG domain of TNX, and they showed that knocking down the α11 subunit blocked TGF-β signaling and EMT. Senior author Ulrich Valcourt now wants to investigate whether the integrin plays an active role in the process or whether it simply docks cells close to the sites where TNX activates latent TGF-β. He also plans to examine the pathway’s role in events that involve TGF-β–induced EMT, such as wound healing and cancer metastasis.
Text by Ben Short