致癌基因调控核苷酸合成在肿瘤中的作用

The role of oncogenes in the regulation of nucleotide biosynthesis in tumorigenesis

肿瘤代谢异常一直是人们关注的焦点。核苷酸作为维持肿瘤细胞快速增殖的必需营养物质,其合成受到多种酶或基因的调控,同时也受其他代谢途径的影响。目前多项研究表明,致癌基因可以通过调控核苷酸的合成来影响肿瘤细胞的增殖,以肿瘤代谢途径为靶点的药物研究越来越多。因此,本文在已有研究的基础上就肿瘤细胞中致癌基因对核苷酸的调控方式及以其为靶点的药物或抑制剂的研究进展作一综述,以期为肿瘤治疗以及靶向药物的开发提供新的思路和策略。

It is well characterized that metabolisms are reprogramed in cancers.As one of the most important metabolic components,the biosynthesis of nucleotide is aberrant in cancer cells.In order to achieve high propagation rate,cancer cells can elevate the rate of nucleotide biosynthesis.One of the mechanisms is through enhancing glucose and glutamine metabolism to produce more molecular precursors required for nucleotide synthesis.Another mechanism is directly to increase the abundance and activity of different rate-limiting enzymesin nucleotide biosynthesis.Considering its importance in tumor generation and development,a number of studies have been taken and have explored that the oncogenes play an important role in the control of nucleotide biosynthesis.Meanwhile,researchers pay more attention to the development of anti-metabolism-related drugs.This review introduces recent progress in oncogenes which can regulate nucleotide biosynthesis,and how glucose and glutamine metabolism is redirected by oncogenes in order to support nucleotide biosynthesis as well as how this pathway is reprogramed.In addition,the targets for cancer therapy by inhibiting the related metabolic enzymes are also discussed.