Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA; Cancer Biology Program, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Biochim Biophys Acta Mol Basis Dis. 2020 Oct 1;1866(10):165841. doi: 10.1016/j.bbadis.2020.165841. Epub 2020 May 19.
Metabolic pathways leading to the synthesis, uptake, and usage of the nonessential amino acid serine are frequently amplified in cancer. Serine encounters diverse fates in cancer cells, including being charged onto tRNAs for protein synthesis, providing head groups for sphingolipid and phospholipid synthesis, and serving as a precursor for cellular glycine and one-carbon units, which are necessary for nucleotide synthesis and methionine cycle reloading. This review will focus on the participation of serine and glycine in the mitochondrial one-carbon (SGOC) pathway during cancer progression, with an emphasis on the genetic and epigenetic determinants that drive SGOC gene expression. We will discuss recently elucidated roles for SGOC metabolism in nucleotide synthesis, redox balance, mitochondrial function, and epigenetic modifications. Finally, therapeutic considerations for targeting SGOC metabolism in the clinic will be discussed.
导致非必需氨基酸丝氨酸合成、摄取和利用的代谢途径在癌症中经常被放大。丝氨酸在癌细胞中会遇到不同的命运，包括被加载到 tRNA 上用于蛋白质合成、为鞘脂和磷脂合成提供头基、以及作为细胞甘氨酸和一碳单位的前体，这些是核苷酸合成和蛋氨酸循环再加载所必需的。本综述将重点讨论丝氨酸和甘氨酸在癌症进展过程中参与线粒体一碳（SGOC）途径的情况，重点讨论驱动 SGOC 基因表达的遗传和表观遗传决定因素。我们将讨论最近阐明的 SGOC 代谢在核苷酸合成、氧化还原平衡、线粒体功能和表观遗传修饰中的作用。最后，将讨论在临床上靶向 SGOC 代谢的治疗考虑。
