Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA.
Redox Biol. 2021 Aug;44:101953. doi: 10.1016/j.redox.2021.101953. Epub 2021 Mar 27.
Controlling reactive oxygen species (ROS) at sustainable levels can drive multiple facets of tumor biology, including within the cancer stem cell (CSC) population. Tight regulation of ROS is one key component in CSCs that drives disease recurrence, cell signaling, and therapeutic resistance. While ROS are well-appreciated to need oxygen and are a product of oxidative phosphorylation, there are also important roles for ROS under hypoxia. As hypoxia promotes and sustains major stemness pathways, further consideration of ROS impacts on CSCs in the tumor microenvironment is important. Furthermore, glycolytic shifts that occur in cancer and may be promoted by hypoxia are associated with multiple mechanisms to mitigate oxidative stress. This altered metabolism provides survival advantages that sustain malignant features, such as proliferation and self-renewal, while producing the necessary antioxidants that reduce damage from oxidative stress. Finally, disease recurrence is believed to be attributed to therapy resistant CSCs which can be quiescent and have changes in redox status. Effective DNA damage response pathways and/or a slow-cycling state can protect CSCs from the genomic catastrophe induced by irradiation and genotoxic agents. This review will explore the delicate, yet complex, relationship between ROS and its pleiotropic role in modulating the CSC.
控制活性氧 (ROS) 处于可持续水平可以驱动肿瘤生物学的多个方面，包括癌症干细胞 (CSC) 群体。ROS 的严格调节是驱动疾病复发、细胞信号转导和治疗抵抗的 CSC 的关键组成部分之一。虽然 ROS 需要氧气并且是氧化磷酸化的产物，但在缺氧下 ROS 也有重要作用。由于缺氧促进和维持主要的干性途径，因此需要进一步考虑肿瘤微环境中 ROS 对 CSCs 的影响。此外，癌症中发生的糖酵解转移，并且可能由缺氧促进，与多种减轻氧化应激的机制相关。这种改变的代谢提供了生存优势，维持了恶性特征，如增殖和自我更新，同时产生必要的抗氧化剂来减少氧化应激造成的损伤。最后，疾病复发被认为归因于对治疗有抗性的 CSCs，这些 CSCs 可以处于静止状态并且具有氧化还原状态的变化。有效的 DNA 损伤反应途径和/或缓慢循环状态可以保护 CSCs 免受辐射和遗传毒性剂诱导的基因组灾难。本综述将探讨 ROS 与调节 CSC 的多效性作用之间的微妙而复杂的关系。
