ArticleFEBS open bio2021
MTHFD2 promotes ovarian cancer growth and metastasis via activation of the STAT3 signaling pathway.
Article in FEBS open bio, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 31 citations in OpenAlex.
- MTHFD2: a promising metabolic checkpoint for diseases.Journal of translational medicine · 2026Review
- Investigating the oncogenic potential of MTHFD2 in oral squamous cell carcinoma.Journal of cancer research and clinical oncology · 2026Article
- NADPH-Related Enzymes and Cancer: Facts and Insights Into the Application of Immunohistochemistry.Biochemistry research international · 2026Review
- MTHFD2 marks pemetrexed resistance in pulmonary adenocarcinoma with EGFR wild type.Discover oncology · 2025Article
- Role of FHOD1 in tumor cells and tumor immune microenvironment.Frontiers in immunology · 2025Review
- EP300-mediated H3 acetylation elevates MTHFD2 expression to reduce mitochondrial dysfunction in lipopolysaccharide-induced tubular epithelial cells.Renal failure · 2024Article
- Interference with MTHFD2 induces ferroptosis in ovarian cancer cells through ERK signaling to suppress tumor malignant progression.Journal of bioenergetics and biomembranes · 2024Article
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- Targeting SHMTs and MTHFDs in cancer: attractive opportunity for anti-tumor strategy.Frontiers in pharmacology · 2024Review
- Identification of microRNA editing sites in clear cell renal cell carcinoma.Scientific reports · 2023Article
- Review
- Identification of MTHFD2 as a prognostic biomarker and ferroptosis regulator in triple-negative breast cancer.Frontiers in oncology · 2023Article
- MTHFD2 is a potential oncogene for its strong association with poor prognosis and high level of immune infiltrates in urothelial carcinomas of bladder.BMC cancer · 2022Article
- ATF4/MYC Regulates MTHFD2 to Promote NSCLC Progression by Mediating Redox Homeostasis.Disease markers · 2022Article
- Folate Transport and One-Carbon Metabolism in Targeted Therapies of Epithelial Ovarian Cancer.Cancers · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) is a bifunctional enzyme located in the mitochondria. MTHFD2 has been reported to be overexpressed in several malignant tumors and is implicated in cancer development. This study aimed to investigate the effect of MTHFD2 on ovarian cancer progression. The expression of MTHFD2 was detected by bioinformatic analysis, immunohistochemistry, RT-qPCR (real-time quantitative PCR analysis), and western blot analysis. The effects of MTHFD2 depletion on cell proliferation, migration, and invasion were determined through in vitro experiments. Cell cycle progression and apoptosis were accessed by flow cytometry. The related signaling pathway protein expression was determined by western blot analysis. We found that MTHFD2 is highly expressed in both ovarian cancer tissues and cell lines. MTHFD2 deletion suppressed cell proliferation and metastasis. Knockdown of MTHFD2 induces cell apoptosis and G2/M arrest, whereas the number of cells in S phase increased with MTHFD2 overexpression. Mechanically, our results indicate that an inhibitory effect of MTHFD2 knockdown may be mediated by the downregulation of cyclin B1/Cdc2 complex and the inhibitory effect on its activity. Additionally, MTHFD2 could regulate cell growth and aggressiveness via activation of STAT3 and the STAT3-induced epithelial-mesenchymal transition signaling pathway. These findings indicate that MTHFD2 is overexpressed in ovarian cancer and regulates cell proliferation and metastasis, presenting an attractive therapeutic target.
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