文章：

Otto Warburg对当前癌症代谢概念的贡献

Otto Warburg's contributions to current concepts of cancer metabolism

原文发布日期：2011-04-14

DOI: 10.1038/nrc3038

类型: Review Article

开放获取: 否

要点：

1. Otto Warburg was a pioneering biochemistry researcher who made substantial contributions to our early understanding of cancer metabolism. Warburg was awarded the Nobel Prize in Physiology or Medicine in 1931 for his discovery of cytochrome c oxidase, not for his work on cancer and the formulation of the Warburg hypothesis.
2. The Warburg effect is the reverse of the Pasteur effect (the inhibition of fermentation by O₂) exhibited by cancer cells; alteration of the Pasteur effect in cancer is linked to prolyl hydroxylases and hypoxia-inducible factor (HIF).
3. Tumour suppressors and oncogenes converge on HIF to reverse the Pasteur effect and thereby induce the Warburg effect.
4. Cancer cells carry out aerobic glycolysis and respiration concurrently.
5. Tumour suppressors and oncogenes exert direct effects on metabolism: p53 promotes the pentose phosphate pathway and oxidative phosphorylation; MYC induces glycolysis and glutamine metabolism.
6. Mutations in metabolic enzymes, specifically isocitrate dehydrogenase 1 (IDH1) and IDH2 and other citric acid cycle enzymes, are causally linked to familial and spontaneous cancers.

要点翻译：

1. 奥托·瓦博格是生物化学研究的先驱，他对早期癌症代谢机制的认知作出了重大贡献。瓦博格因发现细胞色素C氧化酶于1931年获得诺贝尔生理学或医学奖，而非因其在癌症领域提出的瓦博格假说。
2. 瓦博格效应与癌细胞表现的巴斯德效应（氧气对发酵的抑制作用）恰好相反：癌症中巴斯德效应的改变与脯氨酰羟化酶及缺氧诱导因子（HIF）密切相关。
3. 肿瘤抑制因子和致癌基因通过HIF逆转巴斯德效应，从而诱发瓦博格效应。
4. 癌细胞同时进行有氧糖酵解和呼吸作用。
5. 肿瘤抑制因子与致癌基因对代谢产生直接影响：p53促进磷酸戊糖途径和氧化磷酸化过程；MYC诱导糖酵解和谷氨酰胺代谢。
6. 代谢酶突变——特别是异柠檬酸脱氢酶1（IDH1）、IDH2及其他三羧酸循环酶——与遗传性和自发性癌症存在因果关联。

英文摘要：

Otto Warburg pioneered quantitative investigations of cancer cell metabolism, as well as photosynthesis and respiration. Warburg and co-workers showed in the 1920s that, under aerobic conditions, tumour tissues metabolize approximately tenfold more glucose to lactate in a given time than normal tissues, a phenomenon known as the Warburg effect. However, this increase in aerobic glycolysis in cancer cells is often erroneously thought to occur instead of mitochondrial respiration and has been misinterpreted as evidence for damage to respiration instead of damage to the regulation of glycolysis. In fact, many cancers exhibit the Warburg effect while retaining mitochondrial respiration. We re-examine Warburg's observations in relation to the current concepts of cancer metabolism as being intimately linked to alterations of mitochondrial DNA, oncogenes and tumour suppressors, and thus readily exploitable for cancer therapy.

摘要翻译： 

奥托·瓦尔堡（Otto Warburg）率先对癌细胞代谢以及光合作用和呼吸作用进行了定量研究。20世纪20年代，瓦尔堡及其同事发现，在氧气充足的条件下，肿瘤组织在单位时间内将葡萄糖代谢为乳酸的量大约是正常组织的十倍，这一现象被称为“瓦氏效应”（Warburg effect）。然而，人们常常误以为癌细胞中这种有氧糖酵解的增强是替代了线粒体呼吸作用，并将其错误地解释为呼吸作用受损的证据，而非糖酵解调控受损。事实上，许多癌症在表现出瓦氏效应的同时，仍保留了线粒体呼吸功能。我们重新审视瓦尔堡的观察结果，并将其与当前关于癌症代谢的概念联系起来，这些概念认为癌症代谢与线粒体DNA的改变、癌基因和抑癌基因密切相关，因此很容易被用于癌症治疗。

原文链接：

Otto Warburg's contributions to current concepts of cancer metabolism