文章：

从克雷布斯到临床：谷氨酰胺代谢到癌症治疗

From Krebs to clinic: glutamine metabolism to cancer therapy

原文发布日期：2016-07-29

DOI: 10.1038/nrc.2016.71

类型: Review Article

开放获取: 否

要点：

1. Cancer cells show increased consumption of and dependence on glutamine.
2. Glutamine metabolism fuels the tricarboxylic acid (TCA) cycle, nucleotide and fatty acid biosynthesis, and redox balance in cancer cells.
3. Glutamine activates mTOR signalling, suppresses endoplasmic reticulum stress and promotes protein synthesis.
4. Cancer cells may metabolize glutamate to α-ketoglutarate through one of two different pathways (glutamate dehydrogenase or aminotransferases), with aminotransferases potentially supporting a more biosynthetic and pro-growth phenotype.
5. Activation of oncogenic pathways and loss of tumour suppressors reprogramme glutamine metabolism in a tissue-dependent manner.
6. Targeting glutamine metabolism shows promise as an anticancer therapy. Compensatory glutamine metabolism induced by cancer therapies suggests that targeting glutamine metabolism may be used in combination therapy.

要点翻译：

1. 癌细胞对谷氨酰胺的消耗和依赖性增强。
2. 谷氨酰胺代谢为癌细胞的三羧酸循环、核苷酸与脂肪酸生物合成以及氧化还原平衡提供能量。
3. 谷氨酰胺可激活mTOR信号通路，抑制内质网应激并促进蛋白质合成。
4. 癌细胞可能通过两种不同途径（谷氨酸脱氢酶或氨基转移酶）将谷氨酸代谢为α-酮戊二酸，其中氨基转移酶可能支持更具生物合成和促生长特性的表型。
5. 致癌通路的激活与抑癌基因的缺失以组织依赖性方式重编程谷氨酰胺代谢。
6. 靶向谷氨酰胺代谢显示出作为抗癌疗法的潜力。癌症疗法诱导的补偿性谷氨酰胺代谢表明，靶向谷氨酰胺代谢或可应用于联合治疗。

英文摘要：

The resurgence of research into cancer metabolism has recently broadened interests beyond glucose and the Warburg effect to other nutrients, including glutamine. Because oncogenic alterations of metabolism render cancer cells addicted to nutrients, pathways involved in glycolysis or glutaminolysis could be exploited for therapeutic purposes. In this Review, we provide an updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo, and explore the recent potential applications of basic science discoveries in the clinical setting.

摘要翻译： 

癌症代谢研究的复兴最近拓宽了兴趣范围，从葡萄糖和瓦氏效应扩展到包括谷氨酰胺在内的其他营养物质。由于代谢的致癌改变使癌细胞对营养物质上瘾，糖酵解或谷氨酰胺分解所涉及的途径可用于治疗目的。在这篇综述中，我们提供了谷氨酰胺代谢及其在体外和体内参与肿瘤发生的最新概述，并探讨了基础科学发现在临床环境中的近期潜在应用。

原文链接：

From Krebs to clinic: glutamine metabolism to cancer therapy