Department of Zoology, Faculty of Life Sciences, Government College University Faisalabad, Faisalabad, Pakistan.
Department of Physiology, Faculty of Life Sciences, Government College University Faisalabad, Faisalabad, Pakistan.
IUBMB Life. 2018 Nov;70(11):1076-1083. doi: 10.1002/iub.1930. Epub 2018 Aug 29.
Reprogrammed metabolic profile is a biochemical fingerprint of cancerous cells, which represents one of the "hallmarks of cancer." The aberrant expression pattern of enzymatic machineries orchestrates metabolic activities into a platform that ultimately promotes cellular growth, survival, and proliferation. The NADP(+)-dependent mitochondrial malic enzyme 2 (ME2) has been widely appreciated due to its function as a provider of pyruvate and reducing power to the cell for biosynthesis of fatty acids and nucleotides along with maintenance of redox balance. Multiple lines of evidences have indicated that ME2 is a bonafide therapeutic target and novel biomarker which plays critical role during tumorigenesis. The objective of this review is to provide an update on the cancer-specific role of ME2 in order to explore its potential for therapeutic opportunities. Furthermore, we have discussed the potential of genetic and pharmacological inhibitors of ME2 in the light of previous research work for therapeutic advancements in cancer treatment. It is contemplated that additional investigations should focus on the use of ME2 inhibitors in combinational therapies as rational combinations of metabolic inhibitors and chemotherapy may have the ability to cure cancer. © 2018 IUBMB Life, 70(11):1076-1083, 2018.
重编程的代谢特征是癌细胞的生化指纹，这代表了“癌症的标志”之一。酶机制的异常表达模式将代谢活动组织成一个平台，最终促进细胞生长、存活和增殖。由于其作为提供丙酮酸和还原力给细胞的功能，用于脂肪酸和核苷酸的生物合成以及维持氧化还原平衡，NADP(+)-依赖性线粒体苹果酸酶 2（ME2）已被广泛认可。多条证据表明，ME2 是一个真正的治疗靶点和新型生物标志物，在肿瘤发生过程中发挥关键作用。本综述的目的是提供 ME2 在癌症中的特异性作用的最新信息，以探索其在治疗中的潜在机会。此外，我们还根据先前的研究工作讨论了 ME2 的遗传和药理学抑制剂在癌症治疗中的治疗进展的潜力。可以想象，进一步的研究应侧重于 ME2 抑制剂在联合治疗中的应用，因为代谢抑制剂和化疗的合理组合可能有能力治愈癌症。© 2018 IUBMB Life，70(11)：1076-1083，2018。
