Tumour Biology Laboratory, School of Biochemistry and Cell Biology, Bioscience Research Institute, University College Cork, Cork, Ireland.
Tumour Biology Laboratory, School of Biochemistry and Cell Biology, Bioscience Research Institute, University College Cork, Cork, Ireland.
Semin Cell Dev Biol. 2018 Aug;80:50-64. doi: 10.1016/j.semcdb.2017.05.023. Epub 2017 Jun 3.
Increased reactive oxygen species (ROS) production has been detected in various cancers and has been shown to have several roles, for example, they can activate pro-tumourigenic signalling, enhance cell survival and proliferation, and drive DNA damage and genetic instability. Counterintuitively ROS can also promote anti-tumourigenic signalling, initiating oxidative stress-induced tumour cell death. Tumour cells express elevated levels of antioxidant proteins to detoxify elevated ROS levels, establish a redox balance, while maintaining pro-tumourigenic signalling and resistance to apoptosis. Tumour cells have an altered redox balance to that of their normal counterparts and this identifies ROS manipulation as a potential target for cancer therapies. This review discusses the generation and sources of ROS within tumour cells, the regulation of ROS by antioxidant defence systems, as well as the effect of elevated ROS production on their signalling targets in cancer. It also provides an insight into how pro- and anti-tumourigenic ROS signalling pathways could be manipulated in the treatment of cancer.
在各种癌症中已经检测到活性氧(ROS)的产生增加,并已显示其具有多种作用,例如,它们可以激活促肿瘤发生信号,增强细胞存活和增殖,并驱动 DNA 损伤和遗传不稳定性。反直觉的是,ROS 也可以促进抗肿瘤信号,引发氧化应激诱导的肿瘤细胞死亡。肿瘤细胞表达高水平的抗氧化蛋白来解毒升高的 ROS 水平,建立氧化还原平衡,同时保持促肿瘤发生的信号和对细胞凋亡的抵抗。肿瘤细胞的氧化还原平衡与正常细胞不同,这表明 ROS 的操纵可能是癌症治疗的一个潜在靶点。本文综述了肿瘤细胞内 ROS 的产生和来源、抗氧化防御系统对 ROS 的调节,以及升高的 ROS 产生对其在癌症中的信号靶标的影响。它还深入探讨了如何在癌症治疗中操纵促肿瘤和抗肿瘤 ROS 信号通路。