文章：

癌症中糖代谢的重编程：能否用于癌症治疗？

Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy?

原文发布日期：2016-09-16

DOI: 10.1038/nrc.2016.77

类型: Review Article

开放获取: 否

要点：

1. Cancer cells display high aerobic glycolysis despite oxidative phosphorylation.
2. High aerobic glycolysis distinguishes cancer cells from normal cells, and is exploited to detect tumours in vivo.
3. Cancer cells increase glucose flux to meet anabolic demands and to maintain the redox state.
4. Cancer cells preferentially express transporters and enzyme isoforms that drive glucose flux forwards.
5. Selective targeting of glucose metabolism for cancer therapy is challenging, but possible.
6. As a proof of concept, hexokinase 2 (HK2), which is preferentially expressed by cancer cells, can be systemically deleted in mice for cancer therapy and without adverse consequences.
7. It is possible that in the future, targeting glucose metabolism will be used as adjuvant therapy together with existing cancer therapeutic approaches.

要点翻译：

1. 丝氨酸是一种非必需氨基酸，可通过细胞摄取或经丝氨酸合成途径（SSP）从糖酵解中间体从头合成。
2. 丝氨酸参与多种生物合成途径，包括支持核苷酸合成、甲基化反应和抗氧化防御的一碳循环。
3. 尽管一碳代谢酶在线粒体和细胞质中均有表达，但大多数细胞在线粒体中生成甲酸盐用于胞质核苷酸合成。该通路的定向性还能产生线粒体NADH、NADPH和ATP。
4. 部分癌细胞的SSP酶呈现扩增，其存活依赖于这些酶的持续表达——即使在丝氨酸充足条件下亦如此。这似乎反映了维持核苷酸合成对丝氨酸合成的内在需求。
5. 未发生SSP扩增的癌细胞往往依赖外源丝氨酸以实现最佳生长。在丝氨酸匮乏时转向从头合成会导致氧化应激加剧，必须有效调控该过程才能成功适应。
6. 多种癌基因和抑癌基因可调控丝氨酸合成及一碳循环相关酶类，有证据表明其表达与活性的变化会促进恶性肿瘤的发生发展。
7. 目前正在研发基于限制外源丝氨酸或靶向丝氨酸合成/代谢酶的治疗策略。

英文摘要：

In recent years there has been a growing interest among cancer biologists in cancer metabolism. This Review summarizes past and recent advances in our understanding of the reprogramming of glucose metabolism in cancer cells, which is mediated by oncogenic drivers and by the undifferentiated character of cancer cells. The reprogrammed glucose metabolism in cancer cells is required to fulfil anabolic demands. This Review discusses the possibility of exploiting the reprogrammed glucose metabolism for therapeutic approaches that selectively target cancer cells.

摘要翻译： 

近年来，癌症生物学家对癌症代谢的兴趣日益增长。本综述回顾并总结了我们在理解癌细胞葡萄糖代谢重编程方面的过去和最新进展，这种重编程由致癌驱动因子以及癌细胞的未分化特性介导。癌细胞中重编程的葡萄糖代谢是为了满足其合成代谢需求。本综述探讨了利用这种重编程的葡萄糖代谢作为治疗手段的可能性，以选择性地靶向癌细胞。

原文链接：

Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy?