Mitochondrial respiratory defects induces claudin 1 expression via ROS-mediated HSF1 activation

Claudin-1 (Cln-1) are tight junction components that have recently been reported to be involved in cancer metastasis. Interestingly, we found that SNU human hepatoma cells with mitochondrial dysfunction have high level of Cln-1 expression. In those HCC cells, Cln-1 played a key role in regulating invasiveness. Cln-1 expression was also observed in human hepatocellular carcinoma tissues. In this study, we aimed to elucidate how mitochondrial dysfunction is linked with Cln-1 induction. So, we screened whether any specific mitochondrial respiratory defect induces Cln-1 induction. Among diverse respiratory inhibitors, complex I inhibition by rotenone most effectively induced Cln-1 expression at transcriptional level, accompanied by increase in mitochondrial ROS production. Treatment of H2O2 directly induced Cln-1 expression, implying that Cln-1 induction was mediated by mitochondrial ROS. Interestingly, Cln-1 promoter region (-2700bp ~ +300bp) contained transcription factor binding site Heat Shock Factor1 (HSF1), which are known to be regulated by intracellular redox status. Subsequently, we found, that HSF-1 binds to the Cln- 1 promoter. HSF1 knockdown using siRNA decreased Cln-1 expression and invasive activity in SNU449. These results suggest that Cln-1 induced by HSF1 through respiratory defect mediated ROS in hepatoma cells.

Author dc:creator

• 이, 종혁

Contributors dc:contributor

• 윤, 계순
• 대학원 의생명과학과
• 201124446

• Mitochondrial dysfunction
• ROS
• Claudin 1
• HSF 1
• Hepatoma cell
• 간암세포
• 미토콘드리아 기능손상
• 활성산소

Language dc:language

en

Identifier

http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000017595
000000017595

OAI identifier oai:identifier

oai:repository.ajou.ac.kr:201003/10866