Loss of MIG6 Accelerates Initiation and Progression of Mutant Epidermal Growth Factor Receptor–Driven Lung Adenocarcinoma

摘要: Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain drive lung adenocarcinoma. We have previously identified MIG6, an inhibitor of ERBB signaling and a potential tumor suppressor, as target for phosphorylation by mutant EGFRs. Here we demonstrate that Mig6 is suppressor initiation progression EGFR-driven adenocarcinoma mouse models. Mutant EGFR-induced formation was accelerated Mig6-deficient mice, even with haploinsufficiency. constitutive MIG6 at Y394/395 EGFR-mutant human cell lines associated increased interaction EGFR, which may stabilize EGFR protein. also fails to promote degradation. propose model whereby tyrosine decreases its capacity inhibit EGFR. Nonetheless, residual inhibition sufficient delay