ArticleGastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association2021
EPRS/GluRS promotes gastric cancer development via WNT/GSK-3β/β-catenin signaling pathway.
Article in Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
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- Cryo-EM structure of the LARS1:IARS1 complex reveals a nutrient-responsive switch controlling mTORC1 signaling.Nature communications · 2026Article
- PSMD14-mediated PFKFB2 deubiquitination activates H3K27 lactylation to drive cancer stemness in gastric adenocarcinoma.Cell death and differentiation · 2026Article
- Conventional and Novel Approaches to Establishing Mouse Models of Gastric Cancer in the Past, Present, and Potential Post-H. Pylori Infection Era.Biological procedures online · 2026Review
- Dysregulated Proline Metabolism Exacerbates Hepatocellular Carcinoma Metastasis via EPRS1-Mediated mRNA Translation.Cancer communications (London, England) · 2026Article
- Regulating periodontal disease with smart stimuli-responsive systems: Antimicrobial activity, immunomodulation, periodontium regeneration.Materials today. Bio · 2025Review
- GART promotes the proliferation and migration of human non-small cell lung cancer cell lines A549 and H1299 by targeting PAICS-Akt-β-catenin pathway.Frontiers in oncology · 2025Article
- Fisetin may protect early porcine embryos from oxidative stress by down-regulating GRP78 levels.PeerJ · 2025Article
- Combined knockdown of CD151 and MMP9 may inhibit the malignant biological behaviours of triple-negative breast cancer through the GSK-3β/β-catenin-related pathway.Scientific reports · 2024Article
- AKT-dependent nuclear localization of EPRS1 activates PARP1 in breast cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Targeting c-Myc transactivation by LMNA inhibits tRNA processing essential for malate-aspartate shuttle and tumour progression.Clinical and translational medicine · 2024Article
- Evodiamine inhibits EPRS expression to regulate glutamate metabolism and proliferation of oral squamous cell carcinoma cells.The Kaohsiung journal of medical sciences · 2024Article
- Protein-Protein Interactions of Seryl-tRNA Synthetases with Emphasis on Human Counterparts and Their Connection to Health and Disease.Life (Basel, Switzerland) · 2024Review
- Exploring Cuproptosis-Related Genes and Diagnostic Models in Renal Ischemia-Reperfusion Injury Using Bioinformatics, Machine Learning, and Experimental Validation.Journal of inflammation research · 2024Article
- Exploring the Clinical Implications of RPL3 Presence in BRCA-Associated Cancers: Unraveling the Interplay With Cancer Immunity.Clinical Medicine Insights. Oncology · 2024Article
- Functional enrichment analysis of LYSET and identification of related hub gene signatures as novel biomarkers to predict prognosis and immune infiltration status of clear cell renal cell carcinoma.Journal of cancer research and clinical oncology · 2023Article
- Comprehensive analysis of disulfidptosis related genes and prognosis of gastric cancer.World journal of clinical oncology · 2023Article
- Phosphocode-dependent glutamyl-prolyl-tRNA synthetase 1 signaling in immunity, metabolism, and disease.Experimental & molecular medicine · 2023Review
- Control of fibrosis with enhanced safety via asymmetric inhibition of prolyl-tRNA synthetase 1.EMBO molecular medicine · 2023Article
- EPRS1 correlates with malignant progression in hepatocellular carcinoma.Infectious agents and cancer · 2023Article
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
backgroundGlutamyl-prolyl-tRNA synthetase (EPRS/GluRS) is primarily part of the multi-synthetase complex that may play a key role in cancer development. However, the biological function, molecular mechanism, and inhibitor of EPRS have not been investigated in gastric cancer (GC).
methodsImmunohistochemistry was performed to detect the expression of EPRS in human gastric tumor tissues. Knocking down of EPRS, cell-derived xenograft mouse model, and patient-derived xenograft mouse model was used to identify the biological function of EPRS. Immunoprecipitation was applied to elucidate the interaction between EPRS and SCYL2. Computer docking model and multiple in vitro and in vivo experiments were conducted to discover EPRS inhibitors.
resultsHere, we report that EPRS is frequently overexpressed in GC tissues compared to that adjacent controls and its overexpression predicts poor prognosis in GC patients. Functionally, high expression of EPRS positively co-relates with GC development both in vitro and in vivo. Mechanistically, EPRS directly binds with SCYL2 to enhance the activation of WNT/GSK-3β/β-catenin signaling pathway and the accumulation of β-catenin in the nuclear, leading to GC cell proliferation and tumor growth. Moreover, we identified that xanthoangelol (XA) and 4-hydroxyderricin (4-HD) can directly bind to EPRS to block WNT/GSK-3β/β-catenin signaling pathway. More importantly, XA and 4-HD restrain gastric cancer patient-derived xenograft tumor growth and Helicobacter pylori combined with alcohol-induced atrophic gastritis and gastric tumorigenesis.
conclusionThese findings unveil a promising strategy for GC prevention and therapy by targeting EPRS-mediated WNT/GSK-3β/β-catenin cascades. Moreover, XA and 4-HD may be effective reagents used for GC prevention and therapy.
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