The Warburg Effect and the Hallmarks of Cancer

瓦博格效应 氧化磷酸化 线粒体 厌氧糖酵解 糖酵解 细胞外 生物能学 细胞内pH值 癌症 生物 生物化学 细胞生物学 癌细胞 化学 新陈代谢 遗传学
作者
Laurent Schwartz,Claudiu T. Supuran,Khalid O. Alfarouk
出处
期刊:Anti-cancer Agents in Medicinal Chemistry [Bentham Science]
卷期号:17 (2): 164-170 被引量:331
标识
DOI:10.2174/1871520616666161031143301
摘要

It is a longstanding debate whether cancer is one disease or a set of very diverse diseases. The goal of this paper is to suggest strongly that most of (if not all) the hallmarks of cancer could be the consequence of the Warburg‘s effect. As a result of the metabolic impairment of the oxidative phosphorylation, there is a decrease in ATP concentration. To compensate the reduced energy yield, there is massive glucose uptake, anaerobic glycolysis, with an up-regulation of the Pentose Phosphate Pathway resulting in increased biosynthesis leading to increased cell division and local pressure. This increased pressure is responsible for the fractal shape of the tumor, the secretion of collagen by the fibroblasts and plays a critical role in metastatic spread. The massive extrusion of lactic acid contributes to the extracellular acidity and the activation of the immune system. The decreased oxidative phosphorylation leads to impairment in CO2 levels inside and outside the cell, with increased intracellular alkalosis and contribution of carbonic acid to extracellular acidosis-mediated by at least two cancer-associated carbonic anhydrase isoforms. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Mitochondrial disappearance (such as seen in very aggressive tumors) is a consequence of mitochondrial swelling, itself a result of decreased ATP concentration. The transmembrane pumps, which extrude, from the mitochondria, ions, and water, are ATP-dependant. Therapy aiming at increasing both the number and the efficacy of mitochondria could be very useful. Keywords: Warburg’s effect, unification theory, ATP, metabolic treatment, alpha lipoïc acid.
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