The Cross-Talk Between EGFR and E-Cadherin

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.

Automated summary

EGFR and E-cadherin are major regulators of proliferation and differentiation in epithelial cells, and defects in either can lead to malignancies. The reciprocal interactions between EGFR and E-cadherin contribute to tumorigenesis and cancer cell invasion through modulation of adhesion and activity regulation. Understanding the crosstalk between EGFR and E-cadherin is important for tissue morphogenesis, homeostasis, and cancer progression.