从线粒体呼吸到糖酵解的重编程能量产生现在被认为是癌症的标志。当肿瘤生长超过一定尺寸时,它们会引起微环境的变化(例如,缺氧,机械应力)有利于糖酵解的上调。多年来,然而,很明显,糖酵解也可以与肿瘤发生的最早步骤相关联。因此,许多最常参与肿瘤起始和进展的癌蛋白上调糖酵解。此外,近年来,大量的证据已经报道,表明上调糖酵解本身,通过它的酶和/或代谢物,可能在肿瘤发生中起致病作用,通过自身作为致癌刺激物或通过促进致癌突变的出现。事实上,糖酵解上调引起的几种变化已被证明与肿瘤的发生和早期肿瘤发生有关:糖酵解诱导的染色质重塑,抑制早衰和诱导增殖,对DNA修复的影响,目标蛋白的O-连接N-乙酰氨基葡萄糖修饰,抗凋亡作用,诱导上皮-间质转化或自噬,和血管生成的诱导。在本文中,我们总结了上调的糖酵解参与肿瘤启动的证据,在下文中,我们提出了一个机制模型,旨在解释上调的糖酵解如何发挥这样的作用。
Reprogramming energy production from mitochondrial respiration to glycolysis is now considered a hallmark of cancer. When tumors grow beyond a certain size they give rise to changes in their microenvironment (e.g., hypoxia, mechanical stress) that are conducive to the upregulation of glycolysis. Over the years, however, it has become clear that glycolysis can also associate with the earliest steps of tumorigenesis. Thus, many of the oncoproteins most commonly involved in tumor initiation and progression upregulate glycolysis. Moreover, in recent years, considerable evidence has been reported suggesting that upregulated glycolysis itself, through its enzymes and/or metabolites, may play a causative role in tumorigenesis, either by acting itself as an oncogenic stimulus or by facilitating the appearance of oncogenic mutations. In fact, several changes induced by upregulated glycolysis have been shown to be involved in tumor initiation and early tumorigenesis: glycolysis-induced chromatin remodeling, inhibition of premature senescence and induction of proliferation, effects on DNA repair, O-linked N-acetylglucosamine modification of target proteins, antiapoptotic effects, induction of epithelial-mesenchymal transition or autophagy, and induction of angiogenesis. In this article we summarize the evidence that upregulated glycolysis is involved in tumor initiation and, in the following, we propose a mechanistic model aimed at explaining how upregulated glycolysis may play such a role.