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Metabolic scavenging by cancer cells: when the going gets tough the tough keep eating

机译:癌细胞清除代谢的能力:当艰难前进时艰难地继续进食

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摘要

Cancer is fundamentally a disease of uncontrolled cell proliferation. Tumour metabolism has emerged as an exciting new discipline studying how cancer cells obtain the necessary energy and cellular ‘building blocks' to sustain growth. Glucose and glutamine have long been regarded as the key nutrients fuelling tumour growth. However, the inhospitable tumour microenvironment of certain cancers, like pancreatic cancer, causes the supply of these nutrients to be chronically insufficient for the demands of proliferating cancer cells. Recent work has shown that cancer cells are able to overcome this nutrient insufficiency by scavenging alternative substrates, particularly proteins and lipids. Here, we review recent work identifying the endocytic process of macropinocytosis and subsequent lysosomal processing as an important substrate-acquisition route. In addition, we discuss the impact of hypoxia on fatty acid metabolism and the relevance of exogenous lipids for supporting tumour growth as well as the routes by which tumour cells can access these lipids. Together, these cancer-specific scavenging pathways provide a promising opportunity for therapeutic intervention.
机译:癌症从根本上说是一种不受控制的细胞增殖疾病。肿瘤代谢已成为一门令人兴奋的新学科,研究癌细胞如何获得维持生长所需的能量和细胞“基石”。葡萄糖和谷氨酰胺长期以来一直被认为是促进肿瘤生长的关键营养素。但是,某些癌症(如胰腺癌)的难治性肿瘤微环境导致这些营养素的供应长期以来不足以满足增殖癌细胞的需求。最近的工作表明,癌细胞能够通过清除替代性底物(尤其是蛋白质和脂质)来克服这种营养不足的情况。在这里,我们审查最近的工作,确定巨噬细胞的吞噬过程和随后的溶酶体加工作为重要的底物获取途径。此外,我们讨论了缺氧对脂肪酸代谢的影响以及外源脂质对支持肿瘤生长的相关性,以及肿瘤细胞可以访问这些脂质的途径。这些癌症特异性清除途径共同为治疗干预提供了有希望的机会。

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