The sulfiredoxin-peroxiredoxin redox system regulates the stemness and survival of colon cancer stem cells
In-Sung Song,
Yu Jeong Jeong,
Yena Jung,
Young-Ho Park,
Sungbo Shim,
Sung Joo Kim,
Dae-Woon Eom,
Seung-Mo Hong,
Peter C.W. Lee,
Sun-Uk Kim,
Sung-Wuk Jang
Affiliations
In-Sung Song
Department of Biomedical Sciences, College of Medicine, Ulsan University, Asan Medical Center, Seoul, 138-736, Republic of Korea
Yu Jeong Jeong
Department of Biomedical Sciences, College of Medicine, Ulsan University, Asan Medical Center, Seoul, 138-736, Republic of Korea
Yena Jung
Futuristic Animal Resource &Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungchenongbuk-do, 28116, Republic of Korea
Young-Ho Park
Futuristic Animal Resource &Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungchenongbuk-do, 28116, Republic of Korea; Department of Functional Genomics, KRIBB, School of Bioscience, Korea University of Science and Technology, Republic of Korea
Sungbo Shim
Department of Biochemistry, College of Natural Sciences, Chungbuk National University, Cheongju, Republic of Korea
Sung Joo Kim
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea
Dae-Woon Eom
Department of Pathology, Gangneung Asan Hospital, Gangneung, Republic of Korea
Seung-Mo Hong
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea
Peter C.W. Lee
Department of Biomedical Sciences, College of Medicine, Ulsan University, Asan Medical Center, Seoul, 138-736, Republic of Korea
Sun-Uk Kim
Futuristic Animal Resource &Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungchenongbuk-do, 28116, Republic of Korea; Department of Functional Genomics, KRIBB, School of Bioscience, Korea University of Science and Technology, Republic of Korea; Corresponding author. Futuristic Animal Resource &Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungchenongbuk-do, 28116, Republic of Korea.
Sung-Wuk Jang
Department of Biomedical Sciences, College of Medicine, Ulsan University, Asan Medical Center, Seoul, 138-736, Republic of Korea; Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea; Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 138-736, Republic of Korea; Corresponding author. Department of Biomedical Sciences, College of Medicine, Ulsan University, Asan Medical Center, Seoul, 138-736, Republic of Korea.
Cancer stem cells (CSCs) initiate tumor formation and are known to be resistant to chemotherapy. A metabolic alteration in CSCs plays a critical role in stemness and survival. However, the association between mitochondrial energy metabolism and the redox system remains undefined in colon CSCs. In this study, we assessed the role of the Sulfiredoxin-Peroxiredoxin (Srx-Prx) redox system and mitochondrial oxidative phosphorylation (OXPHOS) in maintaining the stemness and survival of colon CSCs. Notably, Srx contributed to the stability of PrxI, PrxII, and PrxIII proteins in colon CSCs. Increased Srx expression promoted the stemness and survival of CSCs and was important for the maintenance of the mitochondrial OXPHOS system. Furthermore, Nrf2 and FoxM1 led to OXPHOS activation and upregulated expression of Srx-Prx redox system-related genes. Therefore, the Nrf2/FoxM1-induced Srx-Prx redox system is a potential therapeutic target for eliminating CSCs in colon cancer.
