Metastatic cells are preferentially vulnerable to lysosomal inhibition.

ABSTRACT: Molecular alterations that confer phenotypic advantages to tumors can also expose specific therapeutic vulnerabilities. To search for potential treatments that would selectively affect metastatic cells, we examined the sensitivity of lineage-related human bladder cancer cell lines with different lung colonization abilities to chloroquine (CQ) or bafilomycin A₁, which are inhibitors of lysosome function and autophagy. Both CQ and bafilomycin A₁ were more cytotoxic in vitro to highly metastatic cells compared with their less metastatic counterparts. Genetic inactivation of macroautophagy regulators and lysosomal proteins indicated that this was due to greater reliance on the lysosome but not upon macroautophagy. To identify the mechanism underlying these effects, we gen

SUBMITTER: Morgan MJ 

PROVIDER: S-EPMC6130375 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature