DDR1 triggers epithelial cell differentiation by promoting cell adhesion through stabilization of E-cadherin

Abstract

Discoidin domain receptor 1 (DDR1) promotes cell differentiation through the increase of E-cadherin-mediated cell-cell contact. Life cell imaging with E-cadherin conjugated with Eos fluorescence protein showed that DDR1 stabilizes membrane-bound E-cadherin and the inactivation of Cdc42 mediates DDR1-regulated cell adhesion and differentiation.

Antitumor activity of 7RH, a discoidin domain receptor 1 inhibitor, alone or in combination with dasatinib exhibits antitumor effects in nasopharyngeal carcinoma cells

“…In addition, adhesion exhibits a crucial function in the formation and maintenance of coherent multicellular structures. DDR1 has previously been demonstrated as one of the key regulators of cell adhesion (31). Therefore, the present study investigated the effect of 7RH on cell-matrix adhesion by performing western blot analysis of cell adhesion-associated proteins and adhesion assays.…”

Cancer Cell Invasion in Three-dimensional Collagen Is Regulated Differentially by Gα13 Protein and Discoidin Domain Receptor 1-Par3 Protein Signaling

“…The collagen-binding protein discoidin domain receptor 1 (DDR1) has been shown to localize to cell-cell junctions and mediate cell-cell adhesion (10,11). In addition to regulating E-cadherin stability at the cell surface (12,13), DDR1, through its interaction with the Par3 polarity complex, can also regulate actin cytoskeleton dynamics (11).…”

“…G␣ 13 , a member of the G 12 family of heterotrimeric G proteins, activates Rho signaling downstream of G protein-coupled receptor activation (14 -16) and has been implicated in cell migration downstream of both G protein-coupled receptors and receptor tyrosine kinases (17). For example, mouse embryonic fibroblasts from G␣ 13 -null mice are deficient in lysophosphatidic acid-stimulated cell migration (18).…”

Integrins and epithelial cell polarity

“…Other ECM receptors, such as the laminin-binding receptor dystroglycan, might contribute to basement membrane deposition and epithelial polarity in some but not all cell types (Esser et al, 2010;Masuda-Hirata et al, 2009;Weir et al, 2006). The collagen-binding discoidin domain receptor is involved in cellcell adhesion and migration, but whether it has a role in polarity is not yet known (Wang et al, 2006;Yeh et al, 2011).…”