View : 939 Download: 262
Ubiquitin C-terminal hydrolase-L1 increases cancer cell invasion by modulating hydrogen peroxide generated via NADPH oxidase 4
- Title
- Ubiquitin C-terminal hydrolase-L1 increases cancer cell invasion by modulating hydrogen peroxide generated via NADPH oxidase 4
- Authors
- Kim, Hyun Jung; Magesh, Venkataraman; Lee, Jae-Jin; Kim, Sun; Knaus, Ulla G.; Lee, Kong-Joo
- Ewha Authors
- 이공주
- SCOPUS Author ID
- 이공주
- Issue Date
- 2015
- Journal Title
- ONCOTARGET
- ISSN
- 1949-2553
- Citation
- ONCOTARGET vol. 6, no. 18, pp. 16287 - 16303
- Keywords
- UCH-L1; ubiquitination; hydrogen peroxide; NOX4; invasion
- Publisher
- IMPACT JOURNALS LLC
- Indexed
- SCIE; SCOPUS
- Document Type
- Article
- Abstract
- This study explored the role of ubiquitin C-terminal hydrolase-L1 (UCH-L1) in the production of ROS and tumor invasion. UCH-L1 was found to increase cellular ROS levels and promote cell invasion. Silencing UCH-L1, as well as inhibition of H2O2 generation by catalase or by DPI, a NOX inhibitor, suppressed the migration potential of B16F10 cells, indicating that UCH-L1 promotes cell migration by up-regulating H2O2 generation. Silencing NOX4, which generates H2O2, with siRNA eliminated the effect of UCH-L1 on cell migration. On the other hand, NOX4 overexpressed in HeLa cells happens to be ubiquitinated, and NOX4 following deubiquitination by UCH-L1, restored H2O2 -generating activity. These in vitro findings are consistent with the results obtained in vivo with catalase (-/-) C57BL/6J mice. When H2O2 and UCH-L1 levels were independently varied in these animals, the former by infecting with H2O2 -scavenging adenovirus-catalase, and the latter by overexpressing or silencing UCH-L1, pulmonary metastasis of B16F10 cells overexpressing UCH-L1 increased significantly in catalase (-/-) mice. In contrast, invasion did not increase when UCH-L1 was silenced in the B16F10 cells. These findings indicate that H2O2 levels regulated by UCH-L1 are necessary for cell invasion to occur and demonstrate that UCH-L1 promotes cell invasion by up-regulating H2O2 via deubiquitination of NOX4.
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
-
001.pdf(1.58 MB)
Download
- Export
- RIS (EndNote)
- XLS (Excel)
- XML