ArticleOncogene2017
Serine hydroxymethyl transferase 1 stimulates pro-oncogenic cytokine expression through sialic acid to promote ovarian cancer tumor growth and progression.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- Amino Acids as Targets for Immunotherapy against Solid Tumors.Cell biochemistry and biophysics · 2026Review
- Tumor suppressor function of SHMT in a Drosophila RasCell death & disease · 2026Article
- Amino acids metabolism: a potential target for cancer treatment.Molecular cancer · 2025Review
- SHMT1, an amino acid metabolism-related gene, is an independent prognostic biomarker in laryngeal squamous cell carcinoma.BMC cancer · 2025Article
- ZNF526 drives tumor growth by enhancing SHMT1-dependent serine metabolism and antioxidant capability in TNBC.Molecular cancer · 2025Article
- Serine metabolism reprogramming in cancer: a multi-tiered regulatory framework.Acta biochimica et biophysica Sinica · 2025Review
- Upregulation of deubiquitinase UBP16 induced by rice stripe virus infection stabilizes SHMT1 to suppress ROS accumulation and facilitate virus infection in Nicotiana benthamiana.Stress biology · 2025Article
- Prediction of Lung Cancer Metastasis Risk Based on Single-Cell Metabolic Profiling of Circulating Tumor Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Multifaceted role of serine hydroxymethyltransferase in health and disease.Molecules and cells · 2025Review
- miR-944 inhibits malignant progression of bladder cancer through ATIC/AKT/FOXO3 A axis mediated by SHMT1.In vitro cellular & developmental biology. Animal · 2025Article
- Integrative bioinformatics approach identifies novel drug targets for hyperaldosteronism, with a focus on SHMT1 as a promising therapeutic candidate.Scientific reports · 2025Article
- Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.Clinical Medicine Insights. Oncology · 2025Review
- Metabolomic Analysis of Histological Composition Variability of High-Grade Serous Ovarian Cancer UsingInternational journal of molecular sciences · 2024Article
- Mixed-phase weak anion-exchange/reversed-phase LC-MS/MS for analysis of nucleotide sugars in human fibroblasts.Analytical and bioanalytical chemistry · 2024Article
- HOXD8 suppresses renal cell carcinoma growth by upregulating SHMT1 expression.Cancer science · 2023Article
- Deregulated Metabolic Pathways in Ovarian Cancer: Cause and Consequence.Metabolites · 2023Review
- Hepatopancreas Proteomic Analysis Reveals Key Proteins and Pathways in Regulatory of Ovary Maturation ofAnimals : an open access journal from MDPI · 2023Article
- Metabolic reprogramming of three major nutrients in platinum-resistant ovarian cancer.Frontiers in oncology · 2023Review
- Comparative proteomics analysis of adultFrontiers in cellular and infection microbiology · 2023Article
- An evolutionarily conserved C4HC3-type E3 ligase regulates plant broad-spectrum resistance against pathogens.The Plant cell · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
High-grade serous (HGS) ovarian cancer accounts for 90% of all ovarian cancer-related deaths. However, factors that drive HGS ovarian cancer tumor growth have not been fully elucidated. In particular, comprehensive analysis of the metabolic requirements of ovarian cancer tumor growth has not been performed. By analyzing The Cancer Genome Atlas mRNA expression data for HGS ovarian cancer patient samples, we observed that six enzymes of the folic acid metabolic pathway were overexpressed in HGS ovarian cancer samples compared with normal ovary samples. Systematic knockdown of all six genes using short hairpin RNAs (shRNAs) and follow-up functional studies demonstrated that serine hydroxymethyl transferase 1 (SHMT1) was necessary for ovarian cancer tumor growth and cell migration in culture and tumor formation in mice. SHMT1 promoter analysis identified transcription factor Wilms tumor 1 (WT1) binding sites, and WT1 knockdown resulted in reduced SHMT1 transcription in ovarian cancer cells. Unbiased large-scale metabolomic analysis and transcriptome-wide mRNA expression profiling identified reduced levels of several metabolites of the amino sugar and nucleotide sugar metabolic pathways, including sialic acid N-acetylneuraminic acid (Neu5Ac), and downregulation of pro-oncogenic cytokines interleukin-6 and 8 (IL-6 and IL-8) as unexpected outcomes of SHMT1 loss. Overexpression of either IL-6 or IL-8 partially rescued SHMT1 loss-induced tumor growth inhibition and migration. Supplementation of culture medium with Neu5Ac stimulated expression of IL-6 and IL-8 and rescued the tumor growth and migratory phenotypes of ovarian cancer cells expressing SHMT1 shRNAs. In agreement with the ovarian tumor-promoting role of Neu5Ac, treatment with Neu5Ac-targeting glycomimetic P-3Fax-Neu5Ac blocked ovarian cancer growth and migration. Collectively, these results demonstrate that SHMT1 controls the expression of pro-oncogenic inflammatory cytokines by regulating sialic acid Neu5Ac to promote ovarian cancer tumor growth and migration. Thus, targeting of SHMT1 and Neu5Ac represents a precision therapy opportunity for effective HGS ovarian cancer treatment.
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