The Cross-Talk Between EGFR and E-Cadherin
Miguel Ramírez Moreno, Natalia A. Bulgakova
Abstract
Epidermal growth factor receptor (EGFR) and adhesion protein E-cadherin are major regulators of proliferation and differentiation in epithelial cells. Consistently, defects in both EGFR and E-cadherin-mediated intercellular adhesion are linked to various malignancies. These defects in either are further exacerbated by the reciprocal interactions between the two transmembrane proteins. On the one hand, EGFR can destabilize E-cadherin adhesion by increasing E-cadherin endocytosis, modifying its interactions with cytoskeleton and decreasing its expression, thus promoting tumorigenesis. On the other hand, E-cadherin regulates EGFR localization and tunes its activity. As a result, loss and mutations of E-cadherin promote cancer cell invasion due to uncontrolled activation of EGFR, which displays enhanced surface motility and changes in endocytosis. In this minireview, we discuss the molecular and cellular mechanisms of the cross-talk between E-cadherin and EGFR, highlighting emerging evidence for the role of endocytosis in this feedback, as well as its relevance to tissue morphogenesis, homeostasis and cancer progression.