Furuta Eiji, Okuda Hiroshi, Kobayashi Aya, Watabe Kounosuke
Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois, USA.
Biochim Biophys Acta. 2010 Apr;1805(2):141-52. doi: 10.1016/j.bbcan.2010.01.005. Epub 2010 Feb 1.
Re-programming of metabolic pathways is a hallmark of physiological changes in cancer cells. The expression of certain genes that directly control the rate of key metabolic pathways including glycolysis, lipogenesis and nucleotide synthesis are drastically altered at different stages of tumor progression. These alterations are generally considered as an adaptation of tumor cells; however, they also contribute to the progression of tumor cells to become more aggressive phenotypes. This review summarizes the recent information about the mechanistic link of these genes to oncogenesis and their potential utility as diagnostic markers as well as for therapeutic targets. We particularly focus on three groups of genes; GLUT1, G6PD, TKTL1 and PGI/AMF in glycolytic pathway, ACLY, ACC1 and FAS in lipogenesis and RRM2, p53R2 and TYMS for nucleotide synthesis. All these genes are highly up-regulated in a variety of tumor cells in cancer patients, and they play active roles in tumor progression rather than expressing merely as a consequence of phenotypic change of the cancer cells. Molecular dissection of their orchestrated networks and understanding the exact mechanism of their expression will provide a window of opportunity to target these genes for specific cancer therapy. We also reviewed existing database of gene microarray to validate the utility of these genes for cancer diagnosis.
代谢途径的重编程是癌细胞生理变化的一个标志。某些直接控制关键代谢途径（包括糖酵解、脂肪生成和核苷酸合成）速率的基因的表达在肿瘤进展的不同阶段会发生显著改变。这些改变通常被认为是肿瘤细胞的一种适应性变化；然而，它们也促使肿瘤细胞发展为更具侵袭性的表型。本综述总结了有关这些基因与肿瘤发生的机制联系以及它们作为诊断标志物和治疗靶点的潜在用途的最新信息。我们特别关注三组基因：糖酵解途径中的GLUT1、G6PD、TKTL1和PGI/AMF，脂肪生成中的ACLY、ACC1和FAS，以及核苷酸合成中的RRM2、p53R2和TYMS。所有这些基因在癌症患者的多种肿瘤细胞中均高度上调，并且它们在肿瘤进展中发挥积极作用，而非仅仅作为癌细胞表型变化的结果而表达。对它们精心编排的网络进行分子剖析并了解其表达的确切机制，将为针对这些基因进行特异性癌症治疗提供契机。我们还查阅了现有的基因微阵列数据库，以验证这些基因在癌症诊断中的效用。
