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Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells

Authors
 Taeho Kwon  ;  Yesol Bak  ;  Young-Ho Park  ;  Gyu-Beom Jang  ;  Jeong-Seok Nam  ;  Jeong Eun Yoo  ;  Young Nyun Park  ;  In Seon Bak  ;  Jin-Man Kim  ;  Do-Young Yoon  ;  Dae-Yeul Yu 
Citation
 STEM CELLS, Vol.34(5) : 1188-1197, 2016 
Journal Title
 STEM CELLS 
ISSN
 1066-5099 
Issue Date
2016
Abstract
Redox regulation in cancer stem cells (CSCs) is viewed as a good target for cancer therapy because redox status plays an important role in cancer stem-cell maintenance. Here, we investigated the role of Peroxiredoxin II (Prx II), an antioxidant enzyme, in association with maintenance of liver CSCs. Our study demonstrates that Prx II overexpressed in liver cancer cells has high potential for self-renewal activity. Prx II expression significantly corelated with expression of epithelial-cell adhesion molecules (EpCAM) and cytokerain 19 in liver cancer tissues of hepatocellular carcinoma (HCC) patients. Downregulation of Prx II in Huh7 cells with treatment of siRNA reduced expression of EpCAM and CD133 as well as Sox2 in accordance with increased ROS and apoptosis, which were reversed in Huh7-hPrx II cells. Huh7-hPrx II cells exhibited strong sphere-formation activity compared with mock cells. Vascular endothelial growth factor (VEGF) exposure enhanced sphere formation, cell-surface expression of EpCAM and CD133, and pSTAT3 along with activation of VEGF receptor 2 in Huh7-hPrx II cells. The result also emerged in Huh7-H-ras(G12V) and SK-HEP-1-H-ras(G12V) cells with high-level expression of Prx II. Prx II was involved in regulation of VEGF driving cancer stem cells through VEGFR-2/STAT3 signaling to upregulate Bmi1 and Sox2. In addition, knockdown of Prx II in Huh7-H-ras(G12V) cells showed significant reduction in cell migration in vitro and in tumorigenic potential in vivo. Taken together, all the results demonstrated that Prx II plays a key role in the CSC self-renewal of HCC cells through redox regulation. Stem Cells 2016;34:1188-1197.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/stem.2323/abstract
DOI
10.1002/stem.2323
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Park, Young Nyun(박영년) ORCID logo https://orcid.org/0000-0003-0357-7967
Yoo, Jeong Eun(유정은)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/152964
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