Mitochondrial Redox Signaling and Tumor Progression.
Mitochondrial Redox Signaling and Tumor Progression.
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DOI：
10.3390/cancers8040040
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发表时间：
2016-03-25
期刊：
影响因子：
5.2
通讯作者：
Min W
中科院分区：
文献类型：
--
作者：
Chen Y;Zhang H;Zhou HJ;Ji W;Min W
癌细胞可以通过将线粒体氧化磷酸化转换为糖酵解来重新编程其能量产生。然而，线粒体在癌细胞中发挥多种作用，包括氧化还原调节、活性氧（ROS）的产生和凋亡信号传导。此外，这些线粒体的作用是通过多种相互关联的代谢和氧化还原敏感途径整合的。有趣的是，线粒体氧化还原蛋白根据细胞ROS水平双相调节肿瘤进展。低水平的ROS作为信号信使，促进癌细胞增殖和癌细胞侵袭。然而，抗癌药物引发的应激信号可以诱导过量的ROS，这对癌细胞是有害的。线粒体氧化还原蛋白可以清除基础ROS，起到“肿瘤抑制因子”的作用，也可以防止过量的ROS起到“肿瘤启动子”的作用。矛盾的是，在癌症进展的各个阶段，过量的ROS往往也会诱导DNA突变和/或促进肿瘤转移。在适当的背景下靶向氧化还原敏感途径和转录因子为癌症的预防和治疗提供了巨大的希望。然而，治疗方法应该是癌症类型和阶段相关的。
Cancer cell can reprogram their energy production by switching mitochondrial oxidative phosphorylation to glycolysis. However, mitochondria play multiple roles in cancer cells, including redox regulation, reactive oxygen species (ROS) generation, and apoptotic signaling. Moreover, these mitochondrial roles are integrated via multiple interconnected metabolic and redox sensitive pathways. Interestingly, mitochondrial redox proteins biphasically regulate tumor progression depending on cellular ROS levels. Low level of ROS functions as signaling messengers promoting cancer cell proliferation and cancer invasion. However, anti-cancer drug-initiated stress signaling could induce excessive ROS, which is detrimental to cancer cells. Mitochondrial redox proteins could scavenger basal ROS and function as “tumor suppressors” or prevent excessive ROS to act as “tumor promoter”. Paradoxically, excessive ROS often also induce DNA mutations and/or promotes tumor metastasis at various stages of cancer progression. Targeting redox-sensitive pathways and transcriptional factors in the appropriate context offers great promise for cancer prevention and therapy. However, the therapeutics should be cancer-type and stage-dependent.