Mitochondrial Respiratory Dysfunction Induces Claudin-1 Expression via Reactive Oxygen Species-mediated Heat Shock Factor 1 Activation, Leading to Hepatoma Cell Invasiveness.

ABSTRACT: Although mitochondrial dysfunction has been implicated in tumor metastasis, it is unclear how it regulates tumor cell aggressiveness. We have reported previously that human hepatoma cells harboring mitochondrial defects have high tumor cell invasion activity via increased claudin-1 (Cln-1) expression. In this study, we demonstrated that mitochondrial respiratory defects induced Cln-1 transcription via reactive oxygen species (ROS)-mediated heat shock factor 1 (HSF1) activation, which contributed to hepatoma invasiveness. We first confirmed the inverse relationship between mitochondrial defects and Cln-1 induction in SNU hepatoma cells and hepatocellular carcinoma tissues. We then examined five different respiratory complex inhibitors, and complex I inhibition by rotenone most effectively i

SUBMITTER: Lee JH 

PROVIDER: S-EPMC4571870 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature