ArticleCellular oncology (Dordrecht, Netherlands)2024
The leukemia inhibitory factor regulates fibroblast growth factor receptor 4 transcription in gastric cancer.
Article in Cellular oncology (Dordrecht, Netherlands), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Pharmacological inhibition of LIF signaling reverses PD-L1-mediated immune suppression in gastric cancer.Translational oncology · 2026Article
- The Farnesoid X receptor-bile acid axis contributes to immune evasion in gastric cancer and its inhibition enhances efficacy of anti-PD-L1 therapy.Biochemistry and biophysics reports · 2026Article
- Tumor-Derived LIF Promotes GDF15-Driven Cachexia and Adverse Outcomes in Gastric Cancer.Cells · 2026Article
- Fgfr4 combined with inflammatory cytokines improves recurrence risk prediction in differentiated thyroid carcinoma: A retrospective cohort study.Journal of medical biochemistry · 2026Article
- FGF19 in Solid Tumors: Molecular Mechanisms, Metabolic Reprogramming, and Emerging Therapeutic Opportunities.Theranostics · 2026Review
- Mesenchymal stem/stromal cells overexpressing leukemia inhibitory factor (LIF) promote arteriogenesis and functional recovery in a mouse model of critical hindlimb ischemia.Stem cell research & therapy · 2025Article
- Harnessing the Estradienone Scaffold to Develop Dual GPBAR1 and LIFR Modulators for Liver Fibrosis.Journal of medicinal chemistry · 2025Article
- Leukemia inhibitory factor promotes human cholangiopathies, and its inhibition improves cholestasis in Abcb4-/- mice.Hepatology communications · 2025Article
- Exploring Boswellia serrata Triterpenes: A New Frontier in Leukemia Inhibitory Factor Receptor Modulation.ACS omega · 2025Article
- Bile acids and their receptors in hepatic immunity.Liver research (Beijing, China) · 2025Review
- Potential signaling pathways, biomarkers, natural drugs, and chronic myeloid leukemia therapeutics.Frontiers in pharmacology · 2025Review
- Bile Acids-Based Therapies for Primary Sclerosing Cholangitis: Current Landscape and Future Developments.Cells · 2024Review
- Identification and Validation of Epithelial Cell Centre Regulatory Transcription Factors in the Gastric Cancer Microenvironment.International journal of general medicine · 2024Article
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Authors and funding
24 authors.
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Abstract
purposeThe gastric adenocarcinoma (GC) represents the third cause of cancer-related mortality worldwide, and available therapeutic options remain sub-optimal. The Fibroblast growth factor receptors (FGFRs) are oncogenic transmembrane tyrosine kinase receptors. FGFR inhibitors have been approved for the treatment of various cancers and a STAT3-dependent regulation of FGFR4 has been documented in the H.pylori infected intestinal GC. Therefore, the modulation of FGFR4 might be useful for the treatment of GC.
methodsTo investigate wich factors could modulate FGFR4 signalling in GC, we employed RNA-seq analysis on GC patients biopsies, human patients derived organoids (PDOs) and cancer cell lines.
resultsWe report that FGFR4 expression/function is regulated by the leukemia inhibitory factor (LIF) an IL-6 related oncogenic cytokine, in JAK1/STAT3 dependent manner. The transcriptomic analysis revealed a direct correlation between the expression of LIFR and FGFR4 in the tissue of an exploratory cohort of 31 GC and confirmed these findings by two external validation cohorts of GC. A LIFR inhibitor (LIR-201) abrogates STAT3 phosphorylation induced by LIF as well as recruitment of pSTAT3 to the promoter of FGFR4. Furthermore, inhibition of FGFR4 by roblitinib or siRNA abrogates STAT3 phosphorylation and oncogentic effects of LIF in GC cells, indicating that FGFR4 is a downstream target of LIF/LIFR complex. Treating cells with LIR-201 abrogates oncogenic potential of FGF19, the physiological ligand of FGFR4.
conclusionsTogether these data unreveal a previously unregnized regulatory mechanism of FGFR4 by LIF/LIFR and demonstrate that LIF and FGF19 converge on the regulation of oncogenic STAT3 in GC cells.
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