了解瓦尔堡效应：细胞增殖的代谢要求,Science

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了解瓦尔堡效应：细胞增殖的代谢要求
Science ( IF 44.7 ) Pub Date : 2009-05-21 , DOI: 10.1126/science.1160809
Matthew G Vander Heiden ₁ , Lewis C Cantley , Craig B Thompson

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生长细胞的燃料经济性 21 世纪对控制细胞生长的信号通路的复杂分析让研究人员回到了 Otto Warburg 的开创性工作，他在 20 年代发现肿瘤细胞以一种不寻常的方式产生能量——通过从线粒体转换呼吸作用到糖酵解。这种代谢转换带来的优势令人费解，因为线粒体呼吸是产生 ATP 的更有效方式。范德·海登等人。（第 1029 页）回顾了以下观点：快速生长的细胞具有超出 ATP 范围的关键代谢需求，更好地了解这些需求可能会为“瓦尔堡效应”带来新的启示，并最终带来新的癌症疗法。正常分化细胞主要依靠线粒体氧化磷酸化来产生细胞过程所需的能量，与之相反，大多数癌细胞依赖于有氧糖酵解，这种现象被称为“瓦尔堡效应”。然而，有氧糖酵解是产生 5'-三磷酸腺苷 (ATP) 的一种低效方式，其给癌细胞带来的优势尚不清楚。在这里，我们提出，癌细胞以及实际上所有增殖细胞的新陈代谢都适应于促进营养物质的吸收和掺入到产生新细胞所需的生物质（例如核苷酸、氨基酸和脂质）中。最近的研究支持了这一观点，表明（i）与细胞增殖有关的几种信号通路也调节将营养物质纳入生物量的代谢途径；(ii) 某些与癌症相关的突变使癌细胞能够以有利于增殖而不是有效产生 ATP 的方式获取和代谢营养物质。更好地了解细胞代谢和生长控制之间的机制联系可能最终会带来更好的人类癌症治疗方法。

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Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

Fuel Economy for Growing Cells Sophisticated 21st-century analyses of the signaling pathways that control cell growth have led researchers back to the seminal work of Otto Warburg, who discovered in the 1920s that tumor cells generate their energy in an unusual way—by switching from mitochondrial respiration to glycolysis. The advantage conferred by this metabolic switch is puzzling because mitochondrial respiration is a more efficient way to produce ATP. Vander Heiden et al. (p. 1029) review arguments that rapidly growing cells have critical metabolic requirements that extend beyond ATP and that a better understanding of these requirements may shed new light on the “Warburg effect” and ultimately lead to new therapies for cancer. In contrast to normal differentiated cells, which rely primarily on mitochondrial oxidative phosphorylation to generate the energy needed for cellular processes, most cancer cells instead rely on aerobic glycolysis, a phenomenon termed “the Warburg effect.” Aerobic glycolysis is an inefficient way to generate adenosine 5′-triphosphate (ATP), however, and the advantage it confers to cancer cells has been unclear. Here we propose that the metabolism of cancer cells, and indeed all proliferating cells, is adapted to facilitate the uptake and incorporation of nutrients into the biomass (e.g., nucleotides, amino acids, and lipids) needed to produce a new cell. Supporting this idea are recent studies showing that (i) several signaling pathways implicated in cell proliferation also regulate metabolic pathways that incorporate nutrients into biomass; and that (ii) certain cancer-associated mutations enable cancer cells to acquire and metabolize nutrients in a manner conducive to proliferation rather than efficient ATP production. A better understanding of the mechanistic links between cellular metabolism and growth control may ultimately lead to better treatments for human cancer.

更新日期：2009-05-21

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