title: Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells.
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.
authors: Disease Model Research Laboratory, Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.|Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors: Taeho
authors: T
authors: Kwon
authors: Disease Model Research Laboratory, Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.|Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors: Yesol
authors: Y
authors: Bak
authors: Disease Model Research Laboratory, Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors: Young-Ho
authors: YH
authors: Park
authors: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors: Gyu-Beom
authors: GB
authors: Jang
authors: School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Korea.
authors: Jeong-Seok
authors: JS
authors: Nam
authors: Department of Pathology, Brain Korea 21 PLUS Project for Medical Science, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors: Jeong Eun
authors: JE
authors: Yoo
authors: Department of Pathology, Brain Korea 21 PLUS Project for Medical Science, Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors: Young Nyun
authors: YN
authors: Park
authors: Disease Model Research Laboratory, Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.|Department of Toxicology Evaluation, Konyang University, Daejeon, Korea.
authors: In Seon
authors: IS
authors: Bak
authors: Department of Pathology, School of Medicine, Chungnam National University, Daejeon, Korea.
authors: Jin-Man
authors: JM
authors: Kim
authors: Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Seoul, Korea.
authors: Do-Young
authors: DY
authors: Yoon
authors: Disease Model Research Laboratory, Aging Intervention Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Korea.
authors: Dae-Yeul
authors: DY
authors: Yu
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000066673:Cell Self Renewal / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D010084:Oxidation-Reduction / Q000187:drug effects; D054464:Peroxiredoxins / Q000378:metabolism*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D050796:STAT3 Transcription Factor; D042461:Vascular Endothelial Growth Factor A; D054464:Peroxiredoxins; D040301:Vascular Endothelial Growth Factor Receptor-2; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Cancer stem cells; Hepatocellular carcinoma; Peroxiredioxin II; Vascular endothelial growth factor