Non-canonical EGFR signaling promotes MAPK-dependent extrusion of epithelial cells.

ABSTRACT: Individual epithelial cells that express oncogenes are often extruded from monolayers of wild-type cells, but the extrusion mechanism is not fully understood. We examined extrusion of mammary epithelial cells caused by induction of oncogenic Ras(Q61L). Ras-dependent extrusion requires phosphorylation of ERK (herein referring to ERK1 and ERK2, also known as MAPK3 and MAPK1, respectively) but not activation of AKT kinases. Unexpectedly, however, extrusion was suppressed by erlotinib, an inhibitor of epidermal growth factor receptor (EGFR), and by deletion of EGFR. In pancreatic and lung cancers, EGFR is required for full activation of Ras. However, EGFR inhibition or deletion had no impact on Ras(Q61L)-GTP levels or ERK phosphorylation. EGFR expression was not required in surrounding wild-ty

SUBMITTER: Molina P 

PROVIDER: S-EPMC12752489 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature