文章：

氧的可用性和代谢适应

Oxygen availability and metabolic adaptations

原文发布日期：2016-09-23

DOI: 10.1038/nrc.2016.84

类型: Review Article

开放获取: 否

要点：

1. Tumour microenvironments harbour multiple microdomains whereby cells experience limited (and highly variable) access to oxygen and nutrients.
2. Oxygen and nutrient availability affect tumour evolution via altered metabolism, blood vessel recruitment, inflammatory cell infiltration and metastasis.
3. Although much of hypoxia research has previously focused on hypoxia-inducible factor (HIF) transcriptional regulators, multiple additional O₂-sensing mechanisms are at play, including those regulated by mTOR complex 1 (mTORC1), endoplasmic reticulum stress responses, autophagy and numerous oxygen-consuming metabolic pathways.
4. The HIFs, as central regulators of metabolic adaptations in hypoxic tumours, significantly influence intracellular metabolism but are also in turn governed by changes in metabolite accumulation.
5. The human genome encodes up to 70 2-oxoglutarate-dependent dioxygenases that probably contribute to tumour phenotypes at the biosynthetic, metabolic, genetic and epigenetic levels.

要点翻译：

1. 肿瘤微环境中存在多个微区域，其中细胞获取氧气和营养的机会有限（且存在高度变异性）。
2. 氧气和营养物质的可用性通过改变代谢、招募血管、炎症细胞浸润和转移等方式影响肿瘤的演化。
3. 尽管此前许多低氧研究主要聚焦于低氧诱导因子（HIF）这一转录调控因子，但实际上还有多种额外的氧感应机制参与其中，包括受mTOR复合物1（mTORC1）调控的机制、内质网应激反应、自噬以及众多耗氧代谢途径。
4. HIF作为低氧肿瘤中代谢适应的核心调控因子，不仅显著影响细胞内代谢，其自身也受代谢物积累变化的调控。
5. 人类基因组编码多达70种2-酮戊二酸依赖的双加氧酶，这些酶可能在生物合成、代谢、遗传和表观遗传层面共同塑造肿瘤表型。

英文摘要：

Oxygen availability, along with the abundance of nutrients (such as glucose, glutamine, lipids and albumin), fluctuates significantly during tumour evolution and the recruitment of blood vessels, leukocytes and reactive fibroblasts to complex tumour microenvironments. As such, hypoxia and concomitant nutrient scarcity affect large gene expression programmes, signalling pathways, diverse metabolic reactions and various stress responses. This Review summarizes our current understanding of how these adaptations are integrated in hypoxic tumour cells and their role in disease progression.

摘要翻译： 

氧气的可利用性，以及葡萄糖、谷氨酰胺、脂质和白蛋白等营养物质的丰度，在肿瘤演进过程中，以及血管、白细胞和反应性成纤维细胞被招募至复杂肿瘤微环境时，会发生显著波动。因此，缺氧并伴随的营养匮乏会影响大规模基因表达程序、信号通路、多种代谢反应和各种应激反应。本综述总结了我们对这些适应性变化如何在缺氧肿瘤细胞中整合，以及它们在疾病进展中所起作用的当前认识。

原文链接：

Oxygen availability and metabolic adaptations