Heterogeneity in Cancer Metabolism: New Concepts in an Old Field.
Heterogeneity in Cancer Metabolism: New Concepts in an Old Field.
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DOI：
10.1089/ars.2016.6750
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发表时间：
2017-03-20
影响因子：
6.6
通讯作者：
Mechta-Grigoriou F
中科院分区：
文献类型：
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作者：
Gentric G;Mieulet V;Mechta-Grigoriou F
意义：在过去的几年里，代谢重编程、生物能量燃料的波动和氧化应激的调节成为肿瘤发展的新关键标志。在癌症中，葡萄糖摄取升高和糖酵解速率高，作为三磷酸腺苷的来源，构成了肿瘤的生长优势。这代表了众所周知的瓦尔堡效应，它催生了使用葡萄糖类似物检测癌细胞的一项主要临床应用：正电子发射断层扫描成像。最新进展：肿瘤中的葡萄糖利用和碳源比最初想象的更加异质。事实上，新的研究出现并揭示了肿瘤细胞具有糖酵解和氧化磷酸化（OXPHOS）代谢的双重能力。 OXPHOS 代谢主要依赖于线粒体呼吸，可对呼吸链复合物进行微调，并增强抗氧化反应或解毒能力。关键问题：OXPHOS 依赖性癌细胞使用替代的可氧化底物，例如谷氨酰胺和脂肪酸。为肿瘤细胞提供燃料的碳底物的多样性表明代谢异质性，即使在具有相同临床诊断的肿瘤内也是如此。代谢转换支持癌细胞干性及其生物能量消耗功能，例如增殖、存活、迁移和侵袭。此外，活性氧诱导的线粒体代谢和营养可用性对于与肿瘤微环境成分的相互作用非常重要。癌相关成纤维细胞和免疫细胞参与与肿瘤细胞的代谢相互作用。它们共同以动态方式适应癌细胞的代谢需求，从而参与肿瘤发生和对治疗的抵抗。未来方向：表征基质细胞、免疫细胞和肿瘤细胞之间的相互代谢相互作用将有助于更好地理解治疗耐药性。抗氧化剂。氧化还原信号。 26、462–485。
Significance: In the last years, metabolic reprogramming, fluctuations in bioenergetic fuels, and modulation of oxidative stress became new key hallmarks of tumor development. In cancer, elevated glucose uptake and high glycolytic rate, as a source of adenosine triphosphate, constitute a growth advantage for tumors. This represents the universally known Warburg effect, which gave rise to one major clinical application for detecting cancer cells using glucose analogs: the positron emission tomography scan imaging. Recent Advances: Glucose utilization and carbon sources in tumors are much more heterogeneous than initially thought. Indeed, new studies emerged and revealed a dual capacity of tumor cells for glycolytic and oxidative phosphorylation (OXPHOS) metabolism. OXPHOS metabolism, which relies predominantly on mitochondrial respiration, exhibits fine-tuned regulation of respiratory chain complexes and enhanced antioxidant response or detoxification capacity. Critical Issues: OXPHOS-dependent cancer cells use alternative oxidizable substrates, such as glutamine and fatty acids. The diversity of carbon substrates fueling neoplastic cells is indicative of metabolic heterogeneity, even within tumors sharing the same clinical diagnosis. Metabolic switch supports cancer cell stemness and their bioenergy-consuming functions, such as proliferation, survival, migration, and invasion. Moreover, reactive oxygen species-induced mitochondrial metabolism and nutrient availability are important for interaction with tumor microenvironment components. Carcinoma-associated fibroblasts and immune cells participate in the metabolic interplay with neoplastic cells. They collectively adapt in a dynamic manner to the metabolic needs of cancer cells, thus participating in tumorigenesis and resistance to treatments. Future Directions: Characterizing the reciprocal metabolic interplay between stromal, immune, and neoplastic cells will provide a better understanding of treatment resistance. Antioxid. Redox Signal. 26, 462–485.