PDF(Pubmed)
Abstract：
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.
摘要：
代谢异常是癌症的标志之一。癌细胞中的代谢模式经过良好的重新编程，为其持续生长提供了基础和能量。在肿瘤代谢重编程过程中，活性氧（ROS）产生和抗氧化系统被激活。高水平的ROS导致氧化损伤甚至细胞死亡，而低水平的ROS充当第二信使来调节许多信号通路。最近,随着氧化应激的重新审视，已经发现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,只有很小一部分的代谢酶，包括甘油醛-3-磷酸脱氢酶(GAPDH)和PKM2等。,据报道经历氧化还原修饰。其他代谢酶是否受氧化还原修饰调节并因此表现出关键功能仍在很大程度上未知。此外，代谢酶的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，是需要解决的关键点。这里,我们将回顾报道的代谢酶的氧化还原修饰模式，涉及的调控机制及其在肿瘤发生和肿瘤进展中的作用。此外,我们将讨论针对肿瘤治疗的代谢酶的氧化还原修饰的未来治疗策略。
