Newman Alice C, Maddocks Oliver D K
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Glasgow G61 1QH, UK.
Br J Cancer. 2017 Jun 6;116(12):1499-1504. doi: 10.1038/bjc.2017.118. Epub 2017 May 4.
Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism.
细胞需要一碳单位用于核苷酸合成、甲基化和还原代谢,而这些途径支持癌细胞的高增殖率。因此,抗叶酸药物(即靶向一碳代谢的药物)长期以来一直用于癌症治疗。氨基酸,如丝氨酸,是主要的一碳来源,癌细胞特别容易受到丝氨酸限制或从头丝氨酸合成抑制导致的一碳单位剥夺的影响。最近的研究也开始阐明对癌细胞一碳代谢重要的特定途径和亚细胞区室。在这篇综述中,我们总结了对癌症中一碳代谢的历史认识,描述了关于一碳单位生成和利用的最新发现,并探索了可能利用癌细胞对一碳代谢的依赖性的未来治疗方法。