Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Mol Cell. 2019 Oct 17;76(2):220-231. doi: 10.1016/j.molcel.2019.09.008. Epub 2019 Oct 2.
Deregulated cell proliferation is an established feature of cancer, and altered tumor metabolism has witnessed renewed interest over the past decade, including the study of how cancer cells rewire metabolic pathways to renew energy sources and "building blocks" that sustain cell division. Microenvironmental oxygen, glucose, and glutamine are regarded as principal nutrients fueling tumor growth. However, hostile tumor microenvironments render O/nutrient supplies chronically insufficient for increased proliferation rates, forcing cancer cells to develop strategies for opportunistic modes of nutrient acquisition. Recent work shows that cancer cells overcome this nutrient scarcity by scavenging other substrates, such as proteins and lipids, or utilizing adaptive metabolic pathways. As such, reprogramming lipid metabolism plays important roles in providing energy, macromolecules for membrane synthesis, and lipid-mediated signaling during cancer progression. In this review, we highlight more recently appreciated roles for lipids, particularly cholesterol and its derivatives, in cancer cell metabolism within intrinsically harsh tumor microenvironments.
细胞增殖失控是癌症的一个既定特征，过去十年中，肿瘤代谢的改变重新引起了人们的兴趣，包括研究癌细胞如何重排代谢途径以更新维持细胞分裂的能源和“构建块”。微环境中的氧气、葡萄糖和谷氨酰胺被认为是促进肿瘤生长的主要营养物质。然而，恶劣的肿瘤微环境使 O/营养供应长期不足，无法满足增殖速度的增加，迫使癌细胞发展出获取营养的机会主义策略。最近的研究表明，癌细胞通过清除其他底物（如蛋白质和脂质）或利用适应性代谢途径来克服这种营养缺乏。因此，脂质代谢的重新编程在为癌症进展过程中的能量、膜合成的大分子以及脂质介导的信号传导提供重要作用。在这篇综述中，我们强调了脂质（特别是胆固醇及其衍生物）在内在恶劣的肿瘤微环境中对癌细胞代谢的作用。
