肿瘤细胞的糖酵解能量代谢机制

Glycolytic Mechanisms in Cancer Cells

肿瘤细胞与正常分化细胞对比有着不同的能量代谢表型,其多通过糖酵解途径消耗更多的葡萄糖,并产生大量的乳酸,却很少利用氧化磷酸化(OXPHOS)进行产能。但肿瘤细胞高糖酵解能量代谢表型的具体分子机制目前尚不完全明确。肿瘤细胞高糖酵解活性可能涉及到糖酵解酶和葡萄糖转运蛋白过表达、OXPHOS酶系和转运蛋白的低表达、线粒体含量减低及DNA对氧化应激的高敏性等机制。然而,肿瘤细胞间遗传、生化和形态学上存在异质性,其升高的糖酵解活性均有自己的不同机制。本文对肿瘤细胞高糖酵解活性的基因和生化调节机制进行具体分析,并讨论肿瘤细胞降低的线粒体代谢和OXPHOS功能的机制。提示肿瘤细胞能量代谢的差异可作为高糖酵解肿瘤细胞的一个治疗靶向。

Tumor cells with altered energy metabolism phenotypes compared with normally differentiated adult cells were found. These tumor cells consume more glucose via the glycolytic pathway and produce more secreted lactate, and rarely use oxidative phosphorylation （ OXPHOS ） to generate more adenosine triphosphate （ P^lrP ）. Nevertheless, the definitive molecular mechanism of the increased glycolysis by this energy metabolism phenotype in the tumor cells remains unclear. The high glycolytic activity of the tumor cells might be involved in the overexpression of glycolytic enzymes and glucose transporters, low OXPHOS expression and transport proteins, as well as the reduced number of mitoehondria per cell and increased mitoehondrial DNA sensitivity to oxidative stress. However, heterogeneity was observed in the genes, the biochemistry, and the morphology of the tumor cells. The elevated glycolytic activity has its own comprehensive mechanism. In this review, we analyzed various genetic and biochemical mechanisms by which tumor cells achieve enhanced glycolytic activity. Furthermore, the proposed mechanisms that lead to decreased mitochondrial metabolism and OXPHOS in tumor cells are also discussed. The energy metabolism system is could be used as an alternative therapeutic target for treating glycolytic tumors.