• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

一碳代谢关键酶：丝氨酸羟甲基转移酶2在癌症中的作用机制及治疗进展

Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.

作者信息

Zhu Siqiang, Liu Yuan, Chen Hao, Zhu Xingyu, Liu Xinyu, Xu Kang, Sang Yaodong, Shang Liang, Chong Wei, Li Leping

机构信息

Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Shandong Provincial Laboratory of Translational Medicine Engineering for Digestive Tumors, Shandong Provincial Hospital, Jinan, China.

出版信息

Clin Med Insights Oncol. 2025 May 6;19:11795549251331755. doi: 10.1177/11795549251331755. eCollection 2025.

DOI:10.1177/11795549251331755
PMID:40337354
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12056339/
Abstract

Serine hydroxymethyltransferase 2 (SHMT2) is a crucial mitochondrial enzyme in 1-carbon (1C) metabolism. It catalyzes the conversion of serine to glycine, generating 1C units essential for purine and pyrimidine synthesis, thereby supporting DNA replication and repair. Abnormally high expression is associated with malignant progression and treatment tolerance in various cancers. This review systematically summarizes the functions of SHMT2 in different types of cancer, underscoring on its roles in metabolism, immune microenvironment, and key signaling pathways (PI3K/AKT/mTOR, JAK-STAT, etc.) and outlines its epigenetic regulation and posttranslational modification mechanisms. Compared with the existing research, we focused on the latest regulatory mechanisms of SHMT2 and its potential in cancer treatment, such as the development and application of small-molecule inhibitors (SHIN2 and AGF347).

摘要

丝氨酸羟甲基转移酶2（SHMT2）是一碳（1C）代谢中一种关键的线粒体酶。它催化丝氨酸转化为甘氨酸，生成嘌呤和嘧啶合成所必需的一碳单位，从而支持DNA复制和修复。异常高表达与多种癌症的恶性进展和治疗耐受性相关。本综述系统总结了SHMT2在不同类型癌症中的功能，强调其在代谢、免疫微环境和关键信号通路（PI3K/AKT/mTOR、JAK-STAT等）中的作用，并概述了其表观遗传调控和翻译后修饰机制。与现有研究相比，我们重点关注了SHMT2的最新调控机制及其在癌症治疗中的潜力，如小分子抑制剂（SHIN2和AGF347）的开发与应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/12056339/db0af7b77a2d/10.1177_11795549251331755-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/12056339/2e4e26d71e58/10.1177_11795549251331755-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/12056339/6214e29fcbb0/10.1177_11795549251331755-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/12056339/4929819aace4/10.1177_11795549251331755-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/12056339/db0af7b77a2d/10.1177_11795549251331755-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/12056339/2e4e26d71e58/10.1177_11795549251331755-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/12056339/6214e29fcbb0/10.1177_11795549251331755-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/12056339/4929819aace4/10.1177_11795549251331755-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/12056339/db0af7b77a2d/10.1177_11795549251331755-fig4.jpg

相似文献

1
Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.一碳代谢关键酶：丝氨酸羟甲基转移酶2在癌症中的作用机制及治疗进展
Clin Med Insights Oncol. 2025 May 6;19:11795549251331755. doi: 10.1177/11795549251331755. eCollection 2025.
2
Role of Mitochondrial and Cytosolic Folylpolyglutamate Synthetase in One-Carbon Metabolism and Antitumor Efficacy of Mitochondrial-Targeted Antifolates.线粒体和细胞质叶酸多聚谷氨酸合成酶在一碳代谢和线粒体靶向抗叶酸药物抗肿瘤疗效中的作用。
Mol Pharmacol. 2024 Sep 17;106(4):173-187. doi: 10.1124/molpharm.124.000912.
3
Roles of Mitochondrial Serine Hydroxymethyltransferase 2 (SHMT2) in Human Carcinogenesis.线粒体丝氨酸羟甲基转移酶2（SHMT2）在人类致癌过程中的作用
J Cancer. 2021 Aug 8;12(19):5888-5894. doi: 10.7150/jca.60170. eCollection 2021.
4
Cellular Pharmacodynamics of a Novel Pyrrolo[3,2-]pyrimidine Inhibitor Targeting Mitochondrial and Cytosolic One-Carbon Metabolism.新型吡咯并[3,2-d]嘧啶抑制剂靶向线粒体和细胞质一碳代谢的细胞药效动力学。
Mol Pharmacol. 2020 Jan;97(1):9-22. doi: 10.1124/mol.119.117937. Epub 2019 Nov 9.
5
Induction of serine hydroxymethyltransferase 2 promotes tumorigenesis and metastasis in neuroblastoma.诱导丝氨酸羟甲基转移酶 2 促进神经母细胞瘤的发生和转移。
Oncotarget. 2022 Jan 6;13:32-45. doi: 10.18632/oncotarget.28168. eCollection 2022.
6
SHMT2 promotes cell viability and inhibits ROS-dependent, mitochondrial-mediated apoptosis via the intrinsic signaling pathway in bladder cancer cells.SHMT2通过内在信号通路促进膀胱癌细胞的细胞活力，并抑制活性氧依赖性、线粒体介导的细胞凋亡。
Cancer Gene Ther. 2022 Oct;29(10):1514-1527. doi: 10.1038/s41417-022-00470-5. Epub 2022 Apr 14.
7
SHMT2 promotes the tumorigenesis of renal cell carcinoma by regulating the m6A modification of PPAT.SHMT2 通过调节 PPAT 的 m6A 修饰促进肾细胞癌的发生。
Genomics. 2022 Jul;114(4):110424. doi: 10.1016/j.ygeno.2022.110424. Epub 2022 Jul 5.
8
Downregulating serine hydroxymethyltransferase 2 (SHMT2) suppresses tumorigenesis in human hepatocellular carcinoma.下调丝氨酸羟甲基转移酶2（SHMT2）可抑制人肝细胞癌的肿瘤发生。
Oncotarget. 2016 Aug 16;7(33):53005-53017. doi: 10.18632/oncotarget.10415.
9
Serine hydroxymethyltransferase 2: a novel target for human cancer therapy.丝氨酸羟甲基转移酶 2：人类癌症治疗的新靶点。
Invest New Drugs. 2021 Dec;39(6):1671-1681. doi: 10.1007/s10637-021-01144-z. Epub 2021 Jul 3.
10
Vital role of SHMT2 in diverse disease.SHMT2 在多种疾病中的重要作用。
Biochem Biophys Res Commun. 2023 Sep 3;671:160-165. doi: 10.1016/j.bbrc.2023.05.108. Epub 2023 May 26.

本文引用的文献

1
Mechanisms and rationales of SAM homeostasis.SAM 稳态的机制与原理。
Trends Biochem Sci. 2025 Mar;50(3):242-254. doi: 10.1016/j.tibs.2024.12.009. Epub 2025 Jan 15.
2
SHIN-2 exerts potent activity against VanA-type vancomycin-resistant Enterococcus faecium in vitro by stabilizing the active site loop of serine hydroxymethyltransferase.SHIN-2 通过稳定丝氨酸羟甲基转移酶的活性位点环对 VanA 型万古霉素耐药粪肠球菌表现出强大的体外活性。
Arch Biochem Biophys. 2024 Nov;761:110160. doi: 10.1016/j.abb.2024.110160. Epub 2024 Sep 21.
3
The direct targets of metformin in diabetes and beyond.
二甲双胍在糖尿病及其他病症中的直接作用靶点。
Trends Endocrinol Metab. 2025 Apr;36(4):364-372. doi: 10.1016/j.tem.2024.07.017. Epub 2024 Sep 2.
4
Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy.Wnt/β-catenin 信号通路在肿瘤发生和癌症治疗中的作用。
J Hematol Oncol. 2024 Jun 18;17(1):46. doi: 10.1186/s13045-024-01563-4.
5
MiR-383-5p inhibits the proliferation and migration of lung adenocarcinoma cells by targeting SHMT2.微小RNA-383-5p通过靶向丝氨酸羟甲基转移酶2抑制肺腺癌细胞的增殖和迁移。
J Cancer. 2024 Mar 17;15(9):2746-2758. doi: 10.7150/jca.89733. eCollection 2024.
6
Mitochondrial and Cytosolic One-Carbon Metabolism Is a Targetable Metabolic Vulnerability in Cisplatin-Resistant Ovarian Cancer.线粒体和细胞质一碳代谢是顺铂耐药卵巢癌的可靶向代谢脆弱性。
Mol Cancer Ther. 2024 Jun 4;23(6):809-822. doi: 10.1158/1535-7163.MCT-23-0550.
7
Unraveling the role of the mitochondrial one-carbon pathway in undifferentiated thyroid cancer by multi-omics analyses.通过多组学分析揭示线粒体一碳途径在未分化甲状腺癌中的作用。
Nat Commun. 2024 Feb 8;15(1):1163. doi: 10.1038/s41467-024-45366-0.
8
SHMT2 promotes papillary thyroid cancer metastasis through epigenetic activation of AKT signaling.丝氨酸羟甲基转移酶2通过AKT信号通路的表观遗传激活促进甲状腺乳头状癌转移。
Cell Death Dis. 2024 Jan 25;15(1):87. doi: 10.1038/s41419-024-06476-1.
9
Cell death.细胞死亡。
Cell. 2024 Jan 18;187(2):235-256. doi: 10.1016/j.cell.2023.11.044.
10
Hypoxia-induced SHMT2 protein lactylation facilitates glycolysis and stemness of esophageal cancer cells.低氧诱导的 SHMT2 蛋白乳酰化促进食管癌的糖酵解和干性。
Mol Cell Biochem. 2024 Nov;479(11):3063-3076. doi: 10.1007/s11010-023-04913-x. Epub 2024 Jan 4.