Reactive oxygen species produced by altered tumor metabolism impacts cancer stem cell maintenance.
Reactive oxygen species produced by altered tumor metabolism impacts cancer stem cell maintenance.
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DOI：
10.1016/j.redox.2021.101953
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发表时间：
2021-08
期刊：
影响因子：
11.4
通讯作者：
Hjelmeland AB
中科院分区：
文献类型：
--
作者：
Tuy K;Rickenbacker L;Hjelmeland AB
将活性氧（ROS）控制在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CSC中驱动疾病复发、细胞信号传导和治疗抗性的一个关键组分。虽然ROS被充分理解为需要氧气并且是氧化磷酸化的产物，但ROS在缺氧下也有重要作用。由于缺氧促进和维持主要的干性途径，进一步考虑活性氧对肿瘤微环境中CSC的影响非常重要。此外，发生在癌症中的糖酵解转变可能由缺氧促进，与减轻氧化应激的多种机制相关。这种改变的代谢提供了生存优势，维持恶性特征，如增殖和自我更新，同时产生必要的抗氧化剂，减少氧化应激造成的损害。最后，疾病复发被认为归因于治疗抗性CSC，其可以是静止的并且具有氧化还原状态的变化。有效的DNA损伤反应途径和/或慢循环状态可以保护CSC免受辐射和遗传毒性剂诱导的基因组灾难。本文将探讨微妙的，但复杂的，ROS和它的多效性的作用，在调制CSC之间的关系。
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.
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DOI：
10.1126/science.1211485
发表时间：
2011-12-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Anastasiou D;Poulogiannis G;Asara JM;Boxer MB;Jiang JK;Shen M;Bellinger G;Sasaki AT;Locasale JW;Auld DS;Thomas CJ;Vander Heiden MG;Cantley LC
通讯作者：
Cantley LC
影响因子：
3.6
作者：
Baskar R;Lee KA;Yeo R;Yeoh KW
通讯作者：
Yeoh KW
影响因子：
4.6
作者：
Bensimon, Julie;Biard, Denis;Lebeau, Jerome
通讯作者：
Lebeau, Jerome
影响因子：
7.8
作者：
Busuttil, RA;Rubio, M;Vijg, J
通讯作者：
Vijg, J
影响因子：
15.9
作者：
Anh Nhat Tran;Walker, Kiera;Hjelmeland, Anita B.
通讯作者：
Hjelmeland, Anita B.