Tenascin-X is the largest member of the tenascin (TN) family of evolutionary conserved extracellular matrix glycoproteins, which also comprises TN-C, TN-R and TN-W. Among this family, TN-X is the only member described so far to exert a crucial architectural function as evidenced by a connective tissue disorder (a recessive form of Ehlers-Danlos syndrome) resulting from a loss-of-function of this glycoprotein in humans and mice. However, TN-X is more than an architectural protein, as it displays features of a matricellular protein by modulating cell adhesion. However, the cellular functions associated with the anti-adhesive properties of TN-X have not yet been revealed. Recent findings indicate that TN-X is also an extracellular regulator of signaling pathways. Indeed, TN-X has been shown to regulate the bioavailability of the Transforming Growth Factor (TGF)-β and to modulate epithelial cell plasticity. The next challenges will be to unravel whether the signaling functions of TN-X are functionally linked to its matricellular properties.
Keywords: ECM, extracellular matrix; EDS, Ehlers-Danlos syndrome; EGF, epidermal growth factor; EMT, epithelial-to-mesenchymal transition; Ehlers-Danlos syndrome (EDS); FAK, focal adhesion kinase; FBG, fibrinogen-like domain; FNIII, fibronectin type III module; LAP, latency associated peptide; MMP, matrix metalloproteinase; SLC, small latent complex; TGF-β; TGF-β activation; TN, tenascin; TSP-1, thrombospondin-1; VEGF, vascular endothelial growth factor; cell signaling; epithelial-to-mesenchymal transition (EMT); integrin α11β1; matricellular protein; tenascin-X; transforming growth factor-β.