E-Cadherin Binding Modulates EGF Receptor Activation

Abstract

We found that E-cadherin and epidermal growth factor receptor (EGFR) are associated in mammary epithelial cells and that E-cadherin engagement in these cells induces transient activation of EGFR, as previously seen in keratinocytes (37). In contrast, EGFR does not associate with and is not activated by N-cadherin. Analysis of cells expressing chimeric cadherins revealed that the extracellular domain of E-cadherin is required for interaction with and activation of EGFR. This activation results in tyrosine phosphorylation of known EGFR substrates and reduction in focal adhesions. These interactions, however, are not necessary for suppression of cell motility by E-cadherin.

E-cadherin-mediated adhesion inhibits ligand-dependent activation of diverse receptor tyrosine kinases

“…E-cadherin is known to form a ligand-independent complex with RTKs (Crepaldi et al, 1994;Hoschuetzky et al, 1994;Pece and Gutkind, 2000). Although b-catenin can bind EGFR or Neu and is a substrate for these RTKs, we found here that ligand-independent complex formation between E-cadherin and EGFR did not depend on E-cadherin binding to b-catenin, a conclusion also made independently by others (Fedor-Chaiken et al, 2003), or on binding to p120-catenin. The correlation with RTK regulation suggests that complex formation between E-cadherin and EGFR may contribute to the effects of E-cadherin on EGFR regulation.…”

Cadherins and cancer: how does cadherin dysfunction promote tumor progression?

“…First, E-cadherin co-accumulates with EGF-R at cell–cell contacts (Fedor-Chaiken et al , 2003) and can physically interact with the EGF receptor (Hoschuetzky et al , 1994; Fedor-Chaiken et al , 2003; Qian et al , 2004) and also with other members of the ErbB receptor tyrosine kinase family (Ochiai et al , 1994). EGF-R did not, however, interact with N-cadherin, suggesting a degree of selectivity among the classical cadherins (Fedor-Chaiken et al , 2003; Qian et al , 2004). The molecular basis for this interaction remains controversial.…”

“…The molecular basis for this interaction remains controversial. Recombinant EGF-R can bind β-catenin in vitro (Hoschuetzky et al , 1994); however, in cells neither the β-catenin- or p120-ctn-binding regions appeared to be necessary for E-cadherin and EGF-R to co-immunoprecipitate (Fedor-Chaiken et al , 2003; Qian et al , 2004). Instead, the interaction appeared to map to the extracellular domain of E-cadherin.…”

Cadherin‐11 binds to PDGFRβ and enhances cell proliferation and tissue regeneration via the PDGFR‐AKT signaling axis

“…13 Although the mechanism underlying the CDH11-mediated regulation of cell proliferation and survival still remains elusive, emerging evidence delineates a new paradigm of heterophilic interactions between cadherins and growth factor receptors may shed a light on it. [14][15][16][17] For instance, N-cadherin (CDH2) was shown to bind to the fibroblast growth factor (FGF) receptor and prevented ligand-induced internalization, thereby sustaining the activity of the FGFR signaling pathway. 17,18 Association of P-cadherin (CDH3) with insulin-like growth | 3793 LIU et aL.…”