Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer
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 a...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2025-05-01
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| Series: | Clinical Medicine Insights: Oncology |
| Online Access: | https://doi.org/10.1177/11795549251331755 |
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| author | Siqiang Zhu Yuan Liu Hao Chen Xingyu Zhu Xinyu Liu Kang Xu Yaodong Sang Liang Shang Wei Chong Leping Li |
| author_facet | Siqiang Zhu Yuan Liu Hao Chen Xingyu Zhu Xinyu Liu Kang Xu Yaodong Sang Liang Shang Wei Chong Leping Li |
| author_sort | Siqiang Zhu |
| collection | DOAJ |
| description | 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). |
| format | Article |
| id | doaj-art-3f1ca12c6f0f40399ac3f46fb7b0ecdf |
| institution | DOAJ |
| issn | 1179-5549 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Clinical Medicine Insights: Oncology |
| spelling | doaj-art-3f1ca12c6f0f40399ac3f46fb7b0ecdf2025-08-20T03:11:33ZengSAGE PublishingClinical Medicine Insights: Oncology1179-55492025-05-011910.1177/11795549251331755Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in CancerSiqiang Zhu0Yuan Liu1Hao Chen2Xingyu Zhu3Xinyu Liu4Kang Xu5Yaodong Sang6Liang Shang7Wei Chong8Leping Li9Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaClinical Research Center of Shandong University, Clinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan, ChinaMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaMedical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, ChinaSerine 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).https://doi.org/10.1177/11795549251331755 |
| spellingShingle | Siqiang Zhu Yuan Liu Hao Chen Xingyu Zhu Xinyu Liu Kang Xu Yaodong Sang Liang Shang Wei Chong Leping Li Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer Clinical Medicine Insights: Oncology |
| title | Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer |
| title_full | Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer |
| title_fullStr | Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer |
| title_full_unstemmed | Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer |
| title_short | Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer |
| title_sort | mechanism and therapeutic progress of one carbon metabolic key enzyme serine hydroxymethyltransferase 2 in cancer |
| url | https://doi.org/10.1177/11795549251331755 |
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