Song In-Sung, Jeong Yu Jeong, Jung Yena, Park Young-Ho, Shim Sungbo, Kim Sung Joo, Eom Dae-Woon, Hong Seung-Mo, Lee Peter C W, Kim Sun-Uk, Jang Sung-Wuk
Department of Biomedical Sciences, College of Medicine, Ulsan University, Asan Medical Center, Seoul, 138-736, Republic of Korea.
Futuristic Animal Resource &Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungchenongbuk-do, 28116, Republic of Korea.
Redox Biol. 2021 Nov 15;48:102190. doi: 10.1016/j.redox.2021.102190.
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.
癌症干细胞（CSCs）启动肿瘤形成，并且已知对化疗具有抗性。CSCs中的代谢改变在干性和存活中起关键作用。然而，线粒体能量代谢与氧化还原系统之间的关联在结肠CSCs中仍不明确。在本研究中，我们评估了硫氧还蛋白-过氧化物酶（Srx-Prx）氧化还原系统和线粒体氧化磷酸化（OXPHOS）在维持结肠CSCs的干性和存活中的作用。值得注意的是，Srx有助于结肠CSCs中PrxI、PrxII和PrxIII蛋白的稳定性。Srx表达增加促进了CSCs的干性和存活，并且对于维持线粒体OXPHOS系统很重要。此外，Nrf2和FoxM1导致OXPHOS激活并上调Srx-Prx氧化还原系统相关基因的表达。因此，Nrf2/FoxM1诱导的Srx-Prx氧化还原系统是消除结肠癌中CSCs的潜在治疗靶点。
