Supplementary Materials Supplemental Material supp_205_3_409__index

Supplementary Materials Supplemental Material supp_205_3_409__index. activation of latent TGF- and following epithelial-to-mesenchymal transition in mammary epithelial cells. Introduction Dynamic cross talk between cells and the surrounding ECM is essential to tissue homeostasis (Nelson and Bissell, 2006). The ECM is usually a network of highly organized macromolecules that are generally large and complex, with multiple Ziyuglycoside II unique domains arranged with specific juxtapositions. Some of these domains interact with cell surface receptors, such as integrins, which mediate cellCmatrix adhesion and transmission transduction into cells (Kim et al., 2011). Matrix molecules can also interact with cellCsurface growth factor receptors or sequester growth factors in the ECM and activate them when needed (Hynes, 2009). The ECM thus acts as an epigenetic informational entity capable of integrating numerous extracellular cues so as to regulate multiple cell phenotypes and behaviors (Kim et al., 2011). The glycoprotein tenascin-X (TNX) is an example of a matrix protein with such a structural and informational role. It belongs Ziyuglycoside II to the tenascin family, whose users (TNC, TNR, TNX, and TNW) share a similar domain name pattern: an N-terminal assembly domain name allowing tenascin oligomerization followed by a series of EGF-like domains, a variable quantity of FNIII (fibronectin type III) modules, and a C-terminal fibrinogen-like (FBG) domain name (Tucker et al., 2006). TNX is usually a Ziyuglycoside II disulfide-linked trimeric protein found in numerous adult tissues. This protein has been shown to interact with ECM components, such as fibrillar (types I, III, and V) and fibril-associated (types XII and XIV) collagens, and the small proteoglycan decorin (Elefteriou et al., 2001; Lethias et Rabbit Polyclonal to OR5B3 al., 2006; Veit et al., 2006; Ziyuglycoside II Egging et al., 2007a). Its impact in ECM network formation and three-dimensional collagen matrix Ziyuglycoside II stiffness (Margaron et al., 2010) is usually supported by the symptoms of the TNX deficiency-related EhlersCDanlos syndrome, a human heritable disorder characterized mainly by joint laxity and skin hyperextensibility (Schalkwijk et al., 2001). TNX has also been described as a matricellular protein, i.e., a protein modulating cellCmatrix interactions. It interacts with cells via two main adhesion sites: a heparin binding site comprising two adjacent FNIII modules, which is a putative ligand for heparan sulfate proteoglycan receptors (Lethias et al., 2001), and the C-terminal FBG domain name, which is the major cell adhesion site of the whole molecule and entails an unidentified 1-made up of integrin receptor (Elefteriou et al., 1999). TNX has also been shown to regulate cell adhesion/deadhesion (Fujie et al., 2009) and thus to inhibit cell distributing in vitro (Elefteriou et al., 1999). In orthotopic experiments conducted on wild-type and TNX-deficient mice, TNX was found to restrain tumor cell invasion and metastasis formation in vivo (Matsumoto et al., 2001). The mechanisms where TNX exerts these natural activities aren’t well understood. To get further insights in to the molecular and mobile systems by which TNX regulates cell migration and invasion, we centered on epithelial cell plasticity. Certainly, several ECM substances have been proven to induce the epithelial-to-mesenchymal changeover (EMT), a cell procedure allowing conversion of polarized, adherent epithelial cells into motile, mesenchymal-like cells (Thiery et al., 2009). For instance, type I collagen induces EMT by regulating diverse signaling cues (Koenig et al., 2006; Shintani et al., 2006, 2008a) and notably the TGF- pathway (Shintani et al., 2008b; DeMaio et al., 2012). TGF- family members (TGF-1, 2, and 3) are synthesized as proproteins and form disulfide-linked homodimers that are proteolytically processed before secretion. Upon cleavage, the prodomain, called the latency-associated peptide (LAP), remains noncovalently bound to the mature (bioactive) TGF- moiety, maintaining it in a.