Journal
REDOX BIOLOGY
Volume 48, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.redox.2021.102190
Keywords
Colon; Cancer stem cell; Sulfiredoxin; Peroxiredoxin; Stemness; ROS; OXPHOS
Categories
Funding
- Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea [2021IL0029-1]
- National Research Foundation of Korea grant - Ministry of Science and ICT [2019R1A2C1090362]
- Basic Science Research Program of the National Research Foundation of Korea - Ministry of Education [2018R1D1A1B07044392, 2020R1A4A1016029]
- Technology Innovation Program - Ministry of Trade, Industry & Energy (MI, Korea) [20009707]
- National Research Foundation of Korea [2020R1A4A1016029, 2019R1A2C1090362, 2018R1D1A1B07044392] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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The study found that the Sulfiredoxin-Peroxiredoxin redox system and mitochondrial oxidative phosphorylation play crucial roles in maintaining the stemness and survival of colon cancer stem cells. The Nrf2/FoxM1-induced Srx-Prx redox system is considered a potential therapeutic target for eliminating CSCs in colon cancer.
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.
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