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.
Highlights
Few components are as determining for cell behaviour and fate as Epidermal Growth Factor Receptor (EGFR), which mediates such diverse processes as cell proliferation, survival, growth and differentiation (Wee and Wang, 2017)
E-cadherin acts in more than one way and in some contexts, may activate EGFR instead. Both EGFR and E-cadherin are vital for normal development, highly dynamic and often dysregulated in cancer cells
There is feedback between the two proteins; EGFR downregulates E-cadherin through multiple mechanisms and vice versa (Figures 2A,B). Such feedback should lead to fast amplification of adhesion loss and EGFR activation, promoting invasiveness and proliferation of a tumour (Figure 2C)
Summary
Few components are as determining for cell behaviour and fate as Epidermal Growth Factor Receptor (EGFR), which mediates such diverse processes as cell proliferation, survival, growth and differentiation (Wee and Wang, 2017). This highlights the importance of understanding the regulation and function of the EGFR signalling for novel cancer therapies (Yarden, 2001; Rowinsky, 2004; Vecchione et al, 2011; Sigismund et al, 2018) Another important component controlling interactions between cells and with their environment is cell adhesion, mediated by Cell Adhesion Molecules (CAMs) (Gumbiner, 1996; Chothia and Jones, 1997). We summarize the existing data on these interactions and highlight the major remaining gaps
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
