Ephrin A1 functions as a ligand of EGFR to promote EMT and metastasis in gastric cancer.

ABSTRACT: Distant metastasis is the major cause of gastric cancer mortality, and epidermal growth factor receptor (EGFR) activation plays critical roles in gastric cancer dissemination. However, EGFR targeting therapies in gastric cancer show only marginal effects, and the molecular mechanisms of oncogenic EGFR signaling remain poorly defined. Here, we report Ephrin A1 as a novel ligand of EGFR in gastric cancer. Ephrin A1 facilitates colonization and metastasis of gastric cancer cells in vitro and in vivo via inducing epithelial-mesenchymal transition (EMT). Ephrin A1 directly interacts with EGFR and induces EGFR dimerization, phosphorylation and activation of downstream signaling. Ephrin A1-induced EMT can be rescued by EGFR signaling inhibitors or knockout of EGFR, but not depletion of its classi

SUBMITTER: Li S 

PROVIDER: S-EPMC11876641 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature