ArticleJournal of experimental & clinical cancer research : CR2018
Up-regulation of FGF15/19 signaling promotes hepatocellular carcinoma in the background of fatty liver.
Article in Journal of experimental & clinical cancer research : CR, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Serum Fibroblast Growth Factor 19 and Total Bile Acid Concentrations Are Potential Biomarkers of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus.BioMed research international · 2020Trial
- The role of FGF19-FGFR4 signaling pathway in liver health and disease: Guardian or destroyer.Genes & diseases · 2026Review
- A Postbiotic-Inducing Ganoderma applanatum Polysaccharide Repairs the Intestinal Barrier via a Phocaeicola vulgatus - Tridecylic Acid Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Evolving Landscape of Systemic Therapy for Hepatocellular Carcinoma: From Targeted Therapy and Combination Strategies to Emerging Therapies.Biomedicines · 2026Review
- Olink Proteomics Analysis Reveals Heterogeneous Responses to FcRn Blockade in Anti-AChR Antibody-Positive Myasthenia Gravis: FGF-19 as a Novel Biomarker.Annals of clinical and translational neurology · 2026Article
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- The roles of nuclear receptors in cholesterol metabolism and reverse cholesterol transport in nonalcoholic fatty liver disease.Hepatology communications · 2024Review
- Klotho in Cancer: Potential Diagnostic and Prognostic Applications.Diagnostics (Basel, Switzerland) · 2023Review
- Zhuyu Pill Alleviates Nonalcoholic Fatty Liver Disease by Regulating Bile Acid Metabolism through the Gut-Liver Axis.ACS omega · 2023Article
- Article
- Wnt/β-Catenin Signaling as a Driver of Stemness and Metabolic Reprogramming in Hepatocellular Carcinoma.Cancers · 2022Review
- Review
- Assessment of fibroblast growth factor 19 as a non-invasive serum marker for hepatocellular carcinoma.World journal of hepatology · 2022Article
- Therapeutic efficacy of lenvatinib in nonviral unresectable hepatocellular carcinoma.JGH open : an open access journal of gastroenterology and hepatology · 2021Article
- Flaxseed Powder Attenuates Non-Alcoholic Steatohepatitis via Modulation of Gut Microbiota and Bile Acid Metabolism through Gut-Liver Axis.International journal of molecular sciences · 2021Article
- The Role of Fibroblast Growth Factor 19 in Hepatocellular Carcinoma.The American journal of pathology · 2021Review
- Fibroblast Growth Factor Receptors (FGFRs) and Noncanonical Partners in Cancer Signaling.Cells · 2021Review
- Ribociclib enhances infigratinib-induced cancer cell differentiation and delays resistance in FGFR-driven hepatocellular carcinoma.Liver international : official journal of the International Association for the Study of the Liver · 2021Article
- High fat diet, gut microbiome and gastrointestinal cancer.Theranostics · 2021Review
- Aberrant FGFR4 signaling worsens nonalcoholic steatohepatitis in FGF21KO mice.International journal of biological sciences · 2021Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundUpregulated fibroblast growth factor 19 (FGF19) expression in human hepatocellular carcinoma (HCC) specimens is associated with tumor progression and poor prognosis. Nonalcoholic steatohepatitis (NASH) patients are at high risk for malignant transformation into HCC.
methodsA steatohepatitis-HCC model was established in male C57L/J mice treated with N-nitrosodiethylamine (DEN) and high-fat diet (HFD). A mouse HCC cell line (Hepa1-6) and a mouse hepatocyte line (FL83B) were used to elucidate the mechanism by free fatty acids (FFA) treatment. FGF15, the mouse orthologue of FGF19, and it receptor fibroblast growth factor receptor4 (FGFR4) as well as co-receptor β-klotho were studied. FGF19 signaling was also studied in human samples of HCC with steatohepatitis.
resultsHCC incidence and tumor volume were significantly increased in the DEN+HFD group compared to that in the DEN+control diet (CD) group. Increased levels of FGF15/FGFR4/β-klotho, aberrant epithelial-mesenchymal transition (EMT) and Wnt/β-catenin signaling were detected in DEN+HFD mice. Blockage of the FGF15 signal can attenuate cell migration ability and aberrant EMT and Wnt/β-catenin signaling.
conclusionsUp-regulated FGF15/FGFR4 signaling promoted the development of HCC by activation of EMT and Wnt/β-catenin signaling in the lipid metabolic disorder microenvironment. Further investigation of FGF19/FGFR4 signaling is important for potential early diagnosis and therapeutic targeting in HCC patients.
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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.