NON-CANONICAL ACTIVATION OF RTKs (EGFR) AND ITS ROLE IN E-CADHERIN JUNCTION DYNAMICS

Abstract

Collective cell migration of epithelial cells drives various fundamental physiological processes, such as wound healing, embryonic morphogenesis, and cancer metastasis. The adherens junction is the central hub controlling collective cell behaviors and its molecular components have been intensively investigated. Yet the molecular mechanism that ensures the homeostasis of junction fluidity during collective cell migration remains elusive. Here, we observed that EGFR is activated in a ligand-independent manner by increasing local junction remodeling during collective cell migration. This EGFR activity, in turn, directs the collective behaviors of cells without affecting single cell motility. The de novo formation of E-cadherin spot adhesion was found to be required for the transient activation of EGFR. EGFR activity then modulates the local junction remodeling during collective cell migration by favoring actin dynamics rather than altering junctional tension. Taken together, these results provide a distinct molecular mechanism linking mechanosignaling to collective cell movements in migrating epithelia.