ArticleJournal of experimental & clinical cancer research : CR2019
SHMT1 inhibits the metastasis of HCC by repressing NOX1-mediated ROS production.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 79 citations in OpenAlex.
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Genetic analysis of cold tolerance and high-altitude adaptation in Gannan indigenous Tibetan sheep through genome-wide scans.BMC genomics · 2026Article
- Tumor suppressor function of SHMT in a Drosophila RasCell death & disease · 2026Article
- From Fly to Human: Translational Relevance ofInternational journal of molecular sciences · 2026Review
- SHMT1, an amino acid metabolism-related gene, is an independent prognostic biomarker in laryngeal squamous cell carcinoma.BMC cancer · 2025Article
- Identification of key factors causing ketosis in dairy cows with low feed intake.Animal biotechnology · 2025Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Genetic variations in amino acid metabolism-related genes are associated with risk of papillary thyroid carcinoma: a case-control study.BMC endocrine disorders · 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
- Suppressor of cytokine signaling 2 modulates regulatory T cell activity to suppress liver hepatocellular carcinoma growth and metastasis.World journal of gastroenterology · 2025Article
- Integrative bioinformatics approach identifies novel drug targets for hyperaldosteronism, with a focus on SHMT1 as a promising therapeutic candidate.Scientific reports · 2025Article
- Poly l-Lactic Acid Nanofiber Membrane Effectively Inhibits Liver Cancer Cells Growth and Prevents Postoperative Residual Cancer Recurrence.ACS applied materials & interfaces · 2025Article
- Mechanism and Therapeutic Progress of One-Carbon Metabolic Key Enzyme: Serine Hydroxymethyltransferase 2 in Cancer.Clinical Medicine Insights. Oncology · 2025Review
- Review
- Cancer-associated fibroblasts derived fibronectin extra domain A promotes sorafenib resistance in hepatocellular carcinoma cells by activating SHMT1.Genes & diseases · 2024Article
- Comprehensive characterization of differential glycation in hepatocellular carcinoma using tissue proteomics with stable isotopic labeling.Analytical and bioanalytical chemistry · 2024Article
- Phosphorylated SHMT2 Regulates Oncogenesis Through mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- A study on the significance of serine hydroxymethyl transferase expression and its role in bladder cancer.Scientific reports · 2024Article
- Identification and validation of key miRNAs and a microRNA-mRNA regulatory network associated with liver cancer.Cell cycle (Georgetown, Tex.) · 2024Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is the most major type of primary hepatic cancer. Serine hydroxymethyltransferase 1 (SHMT1) is recently found to play critical roles in human cancers including lung cancer, ovarian cancer and intestinal cancer. However, the expression, function and the underlying mechanisms of SHMT1 in HCC remain uncovered.
methodsqRT-PCR, immunohistochemistry and immunoblotting were performed to detect the expression of SHMT1 in HCC tissues and cell lines. HCC cell migration and invasion were determined by Boyden chamber and Transwell assay in vitro, and tumor metastasis was assessed via lung metastasis model in mice. The expression of key factors involved in epithelial-to-mesenchymal transition (EMT) process was evaluated by western blotting.
resultsIn this study, data mining of public databases and analysis of clinical specimens demonstrated that SHMT1 expression was decreased in HCC. Reduced SHMT1 level was correlated with unfavorable clinicopathological features and poor prognosis of HCC patients. Gain- and loss-of-function experiments showed that SHMT1 overexpression inhibited the migration and invasion of HCCLM3 cells while SHMT1 knockdown enhanced the metastatic ability of Hep3B cells. Furthermore, qRT-PCR and western blotting showed that SHMT1 inhibited EMT and matrix metallopeptidase 2 (MMP2) expression. In vivo experiments showed that SHMT1 suppressed the lung metastasis of HCC cells in mice. Mechanistically, SHMT1 knockdown enhanced reactive oxygen species (ROS) production, and thus promoted the motility, EMT and MMP2 expression in Hep3B cells. Furthermore, NADPH oxidase 1 (NOX1) was identified to be the downstream target of SHMT1 in HCC. NOX1 expression was negatively correlated with SHMT1 expression in HCC. Rescue experiments revealed that NOX1 mediated the functional influence of SHMT1 on HCC cells.
conclusionsThese data indicate that SHMT1 inhibits the metastasis of HCC by repressing NOX1 mediated ROS production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.