文章：

癌症中代谢水平的改变：对肿瘤生物学和癌症治疗的影响

Altered metabolite levels in cancer: implications for tumour biology and cancer therapy

原文发布日期：2016-09-23

DOI: 10.1038/nrc.2016.85

类型: Review Article

开放获取: 否

要点：

1. Cancer-associated expression changes and mutations in metabolic enzymes can alter levels of metabolites.
2. The accumulation of certain metabolites can support cancer cell proliferation by increasing flux through anabolic metabolism.
3. Competitive inhibition of α-ketoglutarate-dependent dioxygenases by 2-hydroxyglutarate (2HG), succinate and fumarate can promote cancer-associated signalling.
4. Reactive metabolites, such as reactive oxygen species, fumarate, methylglyoxal and fumarylacetoacetate can affect cancer phenotypes.
5. Fumarylacetoacetate is an oncometabolite in the liver of patients with fumarylacetoacetate hydrolase deficiency.
6. Metabolite level alterations in cancer present new opportunities to design novel therapeutics.

要点翻译：

1. 癌症相关的代谢酶表达变化及突变可改变代谢物水平。
2. 特定代谢物的积累能通过增强合成代谢通量促进癌细胞增殖。
3. 2-羟基戊二酸（2HG）、琥珀酸和富马酸对α-酮戊二酸双加氧酶的竞争性抑制作用可激活癌症相关信号通路。
4. 活性代谢物（包括活性氧、富马酸、甲基乙二醛和延胡索酰乙酰乙酸）能够影响癌症表型。
5. 延胡索酰乙酰乙酸作为癌代谢物存在于延胡索酰乙酰乙酸水解酶缺乏症患者的肝脏中。
6. 癌症中代谢物水平的改变为开发新型治疗策略提供了新机遇。

英文摘要：

Altered cell metabolism is a characteristic feature of many cancers. Aside from well-described changes in nutrient consumption and waste excretion, altered cancer cell metabolism also results in changes to intracellular metabolite concentrations. Increased levels of metabolites that result directly from genetic mutations and cancer-associated modifications in protein expression can promote cancer initiation and progression. Changes in the levels of specific metabolites, such as 2-hydroxyglutarate, fumarate, succinate, aspartate and reactive oxygen species, can result in altered cell signalling, enzyme activity and/or metabolic flux. In this Review, we discuss the mechanisms that lead to changes in metabolite concentrations in cancer cells, the consequences of these changes for the cells and how they might be exploited to improve cancer therapy.

摘要翻译： 

细胞代谢改变是许多癌症的特征之一。除了众所周知的营养物质消耗和废物排泄的变化外，癌细胞代谢的改变还会导致细胞内代谢物浓度的变化。由基因突变和癌症相关蛋白表达改变直接导致的代谢物水平升高，可以促进癌症的发生和发展。特定代谢物（如2-羟基戊二酸、延胡索酸、琥珀酸、天冬氨酸和活性氧）水平的变化，可导致细胞信号传导、酶活性和/或代谢通路的改变。在本综述中，我们探讨了导致癌细胞中代谢物浓度变化的机制、这些变化对细胞的影响，以及如何利用这些变化来改善癌症治疗。

原文链接：

Altered metabolite levels in cancer: implications for tumour biology and cancer therapy