Wang Yunqian, Chen Yingxuan, Fang Jingyuan
Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, State Key Laboratory for Oncogenes and Related Genes, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Anticancer Agents Med Chem. 2017 Nov 24;17(11):1456-1465. doi: 10.2174/1871520617666170327110712.
Malignant transformation of cells requires specific adaptations of cellular metabolism to support growth and survival. Alterations in cancer central carbon metabolism including aerobic glycolysis, elevated glutaminolysis, dysregulated tricarboxylic acid cycle and pentose phosphate pathway, facilitate cancer development by maintaining viability and building new biomass. Although a variety of oncogenes or tumor suppressors contribute to these rewiring, accumulating evidence suggests that both post-transcriptional and post-translational modifications (PTMs) also orchestrate the tightly controlled regulation of cancer metabolic adaptations, broadening the biological mechanisms of cancer metabolic reprogramming. Micro RNA, one kind of posttranscriptional modification, mediates transcriptional silencing of various metabolic enzymes. Additional, different kinds of PTMs play important roles in cancer metabolic rewiring by affecting the function, interaction or stability of target proteins. We survey recent studies demonstrating PTMs at lysine residues and microRNAs that are involved in reprogramming of cancer central carbon metabolism, and summarize the effect of these modifications according to different parts of central carbon metabolic pathway. Moreover, we provide an updated overview of the compounds or agents targeting central carbon metabolism in cancer. Given that the heterogeneity of cancer biology, a combination of these novel therapeutics and standard chemotherapeutic agents may obtain better benefit and overcome drug resistance. Finally, this review discusses the challenges and some new steps that may further advance this field.
细胞的恶性转化需要细胞代谢进行特定的适应性改变，以支持生长和存活。癌症中心碳代谢的改变，包括有氧糖酵解、谷氨酰胺分解增加、三羧酸循环失调和磷酸戊糖途径紊乱，通过维持细胞活力和构建新的生物量来促进癌症发展。尽管多种癌基因或肿瘤抑制因子参与了这些代谢重排，但越来越多的证据表明，转录后和翻译后修饰（PTM）也参与了对癌症代谢适应性的严格调控，拓宽了癌症代谢重编程的生物学机制。微小RNA作为一种转录后修饰，介导了各种代谢酶的转录沉默。此外，不同类型的PTM通过影响靶蛋白的功能、相互作用或稳定性，在癌症代谢重排中发挥重要作用。我们综述了近期关于赖氨酸残基的PTM和参与癌症中心碳代谢重编程的微小RNA的研究，并根据中心碳代谢途径的不同部分总结了这些修饰的作用。此外，我们提供了针对癌症中心碳代谢的化合物或药物的最新概述。鉴于癌症生物学的异质性，这些新型疗法与标准化疗药物联合使用可能会获得更好的疗效并克服耐药性。最后，本综述讨论了该领域面临的挑战以及可能进一步推动该领域发展的一些新进展。
