Autophagy is required for crizotinib-induced apoptosis in MET-amplified gastric cancer cells.

ABSTRACT: MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug-sensitive cells in a concentration-dependent manner. We then used chemical and molecular approaches to inhibit autophagy in order to define its role in cell death. The clinically available inhibitor of autophagy, chloroquine, or RNAi-mediated knockdown of two obligate components of the autophagy pathway (AT

SUBMITTER: Schroeder RD 

PROVIDER: S-EPMC5584279 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature