ArticleMolecular carcinogenesis2009
Resident hepatocyte fibroblast growth factor receptor 4 limits hepatocarcinogenesis.
Article in Molecular carcinogenesis, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 47 citations in OpenAlex.
- Endoplasmic reticulum stress at the forefront of fatty liver diseases and cancer.Pharmacological reviews · 2025Review
- Targeting the FGF19-FGFR4 pathway for cholestatic, metabolic, and cancerous diseases.Journal of internal medicine · 2024Review
- Glycosylation of FGFR4 in cholangiocarcinoma regulates receptor processing and cancer signaling.Journal of cellular biochemistry · 2022Article
- The Role of Fibroblast Growth Factor 19 in Hepatocellular Carcinoma.The American journal of pathology · 2021Review
- Role of FGF15 in Hepatic Surgery in the Presence of Tumorigenesis: Dr. Jekyll or Mr. Hyde?Cells · 2021Review
- Metabolic Messengers: FGF21.Nature metabolism · 2021Review
- Editorial: Resident and Ectopic FGF Signaling in Development and Disease.Frontiers in cell and developmental biology · 2020Article
- The Role of Fibroblast Growth Factor 23 in Inflammation and Anemia.International journal of molecular sciences · 2019Review
- FGF9/FGFR2 increase cell proliferation by activating ERK1/2, Rb/E2F1, and cell cycle pathways in mouse Leydig tumor cells.Cancer science · 2018Article
- βKlotho inhibits androgen/androgen receptor‑associated epithelial‑mesenchymal transition in prostate cancer through inactivation of ERK1/2 signaling.Oncology reports · 2018Article
- Emerging roles of FGF signaling in hepatocellular carcinoma.Translational cancer research · 2016Article
- Fibroblast growth factor receptor isotype expression and its association with overall survival in patients with hepatocellular carcinoma.Clinical and molecular hepatology · 2015Article
- Is fibroblast growth factor receptor 4 a suitable target of cancer therapy?Current pharmaceutical design · 2014Review
- Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations.Cancer & metabolism · 2013Article
- Activation of Liver FGF21 in hepatocarcinogenesis and during hepatic stress.BMC gastroenterology · 2013Article
- βKlotho suppresses tumor growth in hepatocellular carcinoma by regulating Akt/GSK-3β/cyclin D1 signaling pathway.PloS one · 2013Article
- FGFR4 and TGF-β1 expression in hepatocellular carcinoma: correlation with clinicopathological features and prognosis.International journal of medical sciences · 2013Article
- Klotho-beta overexpression as a novel target for suppressing proliferation and fibroblast growth factor receptor-4 signaling in hepatocellular carcinoma.Molecular cancer · 2012Article
- Endocrine fibroblast growth factors 15/19 and 21: from feast to famine.Genes & development · 2012Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Fibroblast growth factor (FGF) family signaling mediates cell-to-cell communication in development and organ homeostasis in adults. Of the FGF receptor (FGFR) isotypes, FGFR4 is the sole resident isotype present in mature parenchymal hepatocytes. FGFR1 that is normally associated with activated nonparenchymal cells appears ectopically in hepatoma cells. Ectopic expression and chronic activity of FGFR1 in hepatocytes accelerates diethylnitrosamine (DEN)-initiated hepatocarcinogenesis by driving unrestrained cell proliferation and tumor angiogenesis. Hepatocyte FGFR4 mediates liver's role in systemic cholesterol/bile acid and lipid metabolism and affects proper hepatolobular restoration after damage without effect on cell proliferation. Here we ask whether FGFR4 plays a role in progression of hepatocellular carcinoma (HCC). We report that although spontaneous HCC was not detected in livers of FGFR4-deficient mice, the ablation of FGFR4 accelerated DEN-induced hepatocarcinogenesis. In contrast to FGFR1 that induced a strong mitogenic response and depressed rate of cell death in hepatoma cells, FGFR4 failed to induce a mitogenic response and increased the rate of cell death. FGFR1 but not FGFR4 induced cyclin D1 and repressed p27 expression. Analysis of activation of Erk, JNK, and PI3K-related AKT signaling pathways indicated that in contrast to FGFR1, FGFR4 failed to sustain Erk activation and did not activate AKT. These differences may underlie the opposing effects of FGFR1 and FGFR4. These results suggest that in contrast to ectopic FGFR1 that is a strong promoter of hepatoma, resident FGFR4 that mediates differentiated hepatocyte metabolic functions also serves to suppress hepatoma progression.
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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 Socratic graph.