EGF receptor activates MET through MAPK to enhance non-small cell lung carcinoma invasion and brain metastasis.

ABSTRACT: MET amplification as a mechanism of acquired resistance to EGF receptor (EGFR)-targeted therapies in non-small cell lung carcinoma (NSCLC) led to investigation of novel combinations of EGFR and MET kinase inhibitors. However, promiscuous interactions between MET and ERBB family members have made it difficult to evaluate the effects of MET on EGFR signaling, both independent of drug treatment and in the context of drug resistance. We addressed this issue by establishing a 32D model cell system wherein ERBBs or MET are expressed alone and in combination. Using this model, we determined that EGFR signaling is sufficient to induce MET phosphorylation, although MET activation is enhanced by coexpression of ERBB3. EGFR-MET cross-talk was not direct, but occurred by a combined regulation of MET l

SUBMITTER: Breindel JL 

PROVIDER: S-EPMC3745527 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature