Regulation of claudin-1 mediated hepatoma invasiveness by mitochondrial ROS
Lee, Jong-Hyuk; Lim, Jin J.; Yoon, Gyesoon
Department of Biochemistry & Molecular Biology, Ajou University School of Medicine; Department of Biomedical Sciences, Graduate School of Ajou University
Although mitochondrial dysfunction has been implicated in tumor metastasis, it is unclear how it regulates tumor cell aggressiveness. Previously, we reported 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 activation signal, 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 (HCC) tissues. We then examined five different respiratory complex inhibitors, and complex I inhibition by rotenone most effectively induced Cln-1 at the transcriptional level. Rotenone increased both mitochondrial and cytosolic ROS. In addition, the rotenone-induced Cln-1 expression was attenuated by N-acetyl cysteine, an antioxidant, and exogenous H2O2 treatment was enough to increase Cln-1 transcription, implying the involvement of ROS. Taken together, these results indicate that mitochondrial respiratory defects enhance Cln-1-mediated hepatoma cell invasiveness via mitochondrial ROS-mediated activation signal.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
Total Visit :5,294,302
Total Download :2,237,073
Today View :3,915
Ajou University Medical Information & Media Center 164 Worldcup-ro Yeongtong-gu Suwon 16499 Korea / TEL : 031-219-5312 / FAX : 031-219-5314 Copyright (c) Ajou University Medical Information & Media Center All Rights Reserved. AJOU Open Repository는 국립중앙도서관 OAK 보급사업으로 구축되었습니다.