The Koch Institute for Integrative Cancer Research at Massachusetts Institute of Technology, Cambridge, MA 02139 USA.
Division of Pulmonary and Critical Care Medicine, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 USA.
Cancer Metab. 2014 Nov 28;2:17. doi: 10.1186/2049-3002-2-17. eCollection 2014.
Mitochondria produce reactive oxygen species (mROS) as a natural by-product of electron transport chain activity. While initial studies focused on the damaging effects of reactive oxygen species, a recent paradigm shift has shown that mROS can act as signaling molecules to activate pro-growth responses. Cancer cells have long been observed to have increased production of ROS relative to normal cells, although the implications of this increase were not always clear. This is especially interesting considering cancer cells often also induce expression of antioxidant proteins. Here, we discuss how cancer-associated mutations and microenvironments can increase production of mROS, which can lead to activation of tumorigenic signaling and metabolic reprogramming. This tumorigenic signaling also increases expression of antioxidant proteins to balance the high production of ROS to maintain redox homeostasis. We also discuss how cancer-specific modifications to ROS and antioxidants may be targeted for therapy.
线粒体产生活性氧物质（mROS）是电子传递链活动的一种自然副产物。虽然最初的研究集中在活性氧物质的破坏作用上，但最近的范式转变表明，mROS 可以作为信号分子激活促生长反应。与正常细胞相比，癌细胞一直被观察到具有更高的 ROS 产生，尽管这种增加的意义并不总是清楚。这尤其有趣，因为癌细胞通常也会诱导抗氧化蛋白的表达。在这里，我们讨论了与癌症相关的突变和微环境如何增加 mROS 的产生，这可能导致致癌信号的激活和代谢重编程。这种致癌信号还会增加抗氧化蛋白的表达，以平衡 ROS 的高产生，从而维持氧化还原平衡。我们还讨论了如何针对 ROS 和抗氧化剂的癌症特异性修饰进行治疗。
