Introduction to the molecular basis of cancer metabolism and the Warburg effect
Introduction to the molecular basis of cancer metabolism and the Warburg effect
复制标题
DOI：
10.1007/s11033-015-3857-y
复制
发表时间：
2015-04-01
影响因子：
2.8
通讯作者：
Karagiannis, Tom C.
中科院分区：
文献类型：
--
作者：
Ngo, Darleen C.;Ververis, Katherine;Karagiannis, Tom C.
在分化的正常细胞中，葡萄糖代谢的常规途径涉及糖酵解，随后是柠檬酸循环和电子传递链，以三磷酸腺苷（ATP）的形式产生可用的能量。这发生在氧气的存在下。在缺氧条件下，正常细胞经历无氧糖酵解以产生显著更少的能量，产生乳酸作为产物。正如奥托瓦尔堡在20世纪20年代首次强调的那样，肿瘤细胞表现出的代谢涉及有氧糖酵解速率的增加，称为瓦尔堡效应。在有氧糖酵解中，即使在氧气存在下，糖酵解产生的丙酮酸分子也转化为较少的ATP分子。有证据表明，肿瘤细胞进行有氧糖酵解的原因包括：（1）优先级转移到积累生物量而不是能量生产，（2）由于线粒体释放的活性氧较少，从而逃避细胞凋亡，以及（3）产生乳酸盐以进一步促进肿瘤生长。在这篇简短的综述中，我们讨论了癌症代谢和瓦尔堡效应的新兴分子方面。瓦尔堡效应的各个方面进行了分析的背景下，已建立的标志性癌症，包括癌基因和肿瘤抑制基因的作用。
In differentiated normal cells, the conventional route of glucose metabolism involves glycolysis, followed by the citric acid cycle and electron transport chain to generate usable energy in the form of adenosine triphosphate (ATP). This occurs in the presence of oxygen. In hypoxic conditions, normal cells undergo anaerobic glycolysis to yield significantly less energy producing lactate as a product. As first highlighted in the 1920s by Otto Warburg, the metabolism exhibited by tumor cells involves an increased rate of aerobic glycolysis, known as the Warburg effect. In aerobic glycolysis, pyruvate molecules yielded from glycolysis are converted into fewer molecules of ATP even in the presence of oxygen. Evidence indicates that the reasons as to why tumor cells undergo aerobic glycolysis include: (1) the shift in priority to accumulate biomass rather than energy production, (2) the evasion of apoptosis as fewer reactive oxygen species are released by the mitochondria and (3) the production of lactate to further fuel growth of tumors. In this mini-review we discuss emerging molecular aspects of cancer metabolism and the Warburg effect. Aspects of the Warburg effect are analyzed in the context of the established hallmarks of cancer including the role of oncogenes and tumor suppressor genes.