The Roles of Reactive Oxygen Species and Autophagy in Mediating the Tolerance of Tumor Cells to Cycling Hypoxia
The Roles of Reactive Oxygen Species and Autophagy in Mediating the Tolerance of Tumor Cells to Cycling Hypoxia
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DOI：
10.1016/j.semradonc.2013.05.006
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发表时间：
2013-10-01
影响因子：
3.5
通讯作者：
Wouters, Bradly G.
中科院分区：
文献类型：
--
作者：
Koritzinsky, Marianne;Wouters, Bradly G.
肿瘤缺氧（低氧合）会导致治疗抵抗和患者预后不佳。相当一部分肿瘤细胞经历循环性缺氧，其特征是短暂的缺氧和复氧。这些细胞承受着独特的压力负担，这是由活性氧（ROS）的过量产生介导的。 ROS 损伤的细胞成分可以通过自噬清除，使循环缺氧的肿瘤细胞特别容易受到自噬及其上游调节途径的抑制。缺氧期间未折叠蛋白反应的 PERK 介导的信号臂的激活在防御 ROS 中发挥着关键作用，既通过刺激谷胱甘肽合成途径，又通过促进自噬。 Semin Radiat Oncol 23:252-261 (C) 2013 爱思唯尔公司出版
Tumor hypoxia (low oxygenation) causes treatment resistance and poor patient outcome. A substantial fraction of tumor cells experience cycling hypoxia, characterized by transient episodes of hypoxia and reoxygenation. These cells are under a unique burden of stress, mediated by excessive production of reactive oxygen species (ROS). Cellular components damaged by ROS can be cleared by autophagy, rendering cycling hypoxic tumor cells particularly vulnerable to inhibition of autophagy and its upstream regulatory pathways. Activation of the PERK-mediated signaling arm of the unfolded protein response during hypoxia plays a critical role in the defense against ROS, both by stimulating glutathione synthesis pathways and through promoting autophagy. Semin Radiat Oncol 23:252-261 (C) 2013 Published by Elsevier Inc.