Wang Kui, Ming Hui, Zuo Jing, Tian Hai-Long, Huang Can-Hua
Collaborative Innovation Center for Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.
West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu 610041, China.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2021 Jan;52(1):57-63. doi: 10.12182/20210160204.
Metabolic aberrance is one of the hallmarks of cancer. The metabolic patterns in cancer cells are well reprogrammed to provide building blocks and energy for their sustained growth. During tumor metabolic reprogramming, reactive oxygen species (ROS) are generated and the antioxidant systems are activated. High levels of ROS lead to oxidative damage and even cell death, whereas ROS at low levels act as second messenger to regulate many signaling pathways. Recently, with the revisiting of oxidative stress, it has been found that ROS can directly mediate the redox modifications of proteins, resulting in protein conformational and functional alterations. However, only a very small portion of metabolic enzymes, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and PKM2, etc., has been reported to undergo redox modifications. Whether other metabolic enzymes are regulated by redox modifications and thus exhibit critical functions remain largely unknown. Moreover, the specific spatio-temporal targeting of redox modifications of metabolic enzymes, as well as overcoming the existed redox and metabolic adaptation, are key points to be solved. Here, we will review the reported redox modification patterns of metabolic enzymes, the involved regulatory mechanisms and their roles in tumorigenesis and tumor progress. In addition, we will discuss the future therapeutic strategies targeting redox modifications of metabolic enzymes for tumor treatment.
代谢异常是癌症的标志之一。癌细胞中的代谢模式被重新编程，以提供其持续生长所需的结构单元和能量。在肿瘤代谢重编程过程中，会产生活性氧（ROS），同时抗氧化系统被激活。高水平的ROS会导致氧化损伤甚至细胞死亡，而低水平的ROS则作为第二信使调节许多信号通路。最近，随着对氧化应激的重新审视，发现ROS可以直接介导蛋白质的氧化还原修饰，导致蛋白质构象和功能改变。然而，据报道只有极少数代谢酶，包括甘油醛-3-磷酸脱氢酶（GAPDH）和丙酮酸激酶M2（PKM2）等，会发生氧化还原修饰。其他代谢酶是否受氧化还原修饰调控并因此发挥关键作用，在很大程度上仍不清楚。此外，代谢酶氧化还原修饰的特定时空靶向，以及克服现有的氧化还原和代谢适应，是有待解决的关键问题。在此，我们将综述已报道的代谢酶氧化还原修饰模式、相关调控机制及其在肿瘤发生和进展中的作用。此外，我们还将讨论针对代谢酶氧化还原修饰的未来肿瘤治疗策略。
