Department of Pathology, Xuzhou Medical University, 209 Tong-shan Road, Xuzhou, 221004, Jiangsu, China.
Invest New Drugs. 2021 Dec;39(6):1671-1681. doi: 10.1007/s10637-021-01144-z. Epub 2021 Jul 3.
Serine and glycine are the primary sources of one-carbon units that are vital for cell proliferation. Their abnormal metabolism is known to be associated with cancer progression. As the key enzyme of serine metabolism, Serine Hydroxymethyltransferase 2 (SHMT2) has been a research hotspot in recent years. SHMT2 is a PLP-dependent tetrameric enzyme that catalyzes the reversible transition from serine to glycine, thus promoting the production of one-carbon units that are indispensable for cell growth and regulation of the redox and epigenetic states of cells. Under a hypoxic environment, SHMT2 can be upregulated and could promote the generation of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione for maintaining the redox balance. Accumulating evidence confirmed that SHMT2 facilitates cell proliferation and tumor growth and is tightly associated with poor prognosis. In this review, we present insights into the function and research development of SHMT2 and summarize the possible molecular mechanisms of SHMT2 in promoting tumor growth, in the hope that it could provide clues to more effective clinical treatment of cancer.
丝氨酸和甘氨酸是一碳单位的主要来源，一碳单位对细胞增殖至关重要。已知它们的异常代谢与癌症的进展有关。丝氨酸羟甲基转移酶 2（SHMT2）作为丝氨酸代谢的关键酶，近年来已成为研究热点。SHMT2 是一种依赖 PLP 的四聚体酶，可催化丝氨酸到甘氨酸的可逆转化，从而促进一碳单位的产生，一碳单位是细胞生长所必需的，并且调节细胞的氧化还原和表观遗传状态。在低氧环境下，SHMT2 可被上调，并可促进烟酰胺腺嘌呤二核苷酸磷酸（NADPH）和谷胱甘肽的产生，以维持氧化还原平衡。越来越多的证据证实，SHMT2 促进细胞增殖和肿瘤生长，与不良预后密切相关。本综述介绍了 SHMT2 的功能和研究进展，并总结了 SHMT2 促进肿瘤生长的可能分子机制，希望为癌症的更有效临床治疗提供线索。
