Cell migration signaling through the EGFR-VAV2-Rac1 pathway is sustained in endosomes.

ABSTRACT: Ligand binding to EGFR activates Rho family GTPases, triggering actin cytoskeleton reorganization, cell migration and invasion. Activated EGFR is also rapidly endocytosed but the role of EGFR endocytosis in cell motility is poorly understood. Hence, we used live-cell microscopy imaging to demonstrate that endogenous fluorescently labeled VAV2, a guanine nucleotide exchange factor for Rho GTPases, is co-endocytosed with EGFR in genome-edited human oral squamous cell carcinoma (HSC3) cells, an in vitro model for head-and-neck cancer where VAV2 is known to promote metastasis and is associated with poor prognosis. Chemotactic migration of HSC3 cells toward an EGF gradient is found to require both VAV2 and clathrin-mediated endocytosis. Moreover, sustained activation of Rac1, a Rho family GTPas

SUBMITTER: Pinilla-Macua I 

PROVIDER: S-EPMC11828472 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature