ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2016
Mice with hepatocyte-specific FXR deficiency are resistant to spontaneous but susceptible to cholic acid-induced hepatocarcinogenesis.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Using proton pump inhibitors increases the risk of hepato-biliary-pancreatic cancer. A systematic review and meta-analysis.Frontiers in pharmacology · 2022Pooled it
- The gut microbiome-bile acid-FXR interplay: a pivotal axis in metabolic and gastrointestinal diseases.Gut microbes · 2026Review
- Bile acids as a "new hormone" in aging-related liver disease.Life medicine · 2026Review
- Farnesoid x Receptor Deficiency Promotes Hepatocytic Injury in Cyp2c70-Deficient Mice With a Human-Like Bile Acid Composition.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Transcriptional and Post-Transcriptional Anticholestatic Mechanisms of Obeticholic Acid in Lipopolysaccharide-Induced Cholestasis.Pharmaceutics · 2025Article
- Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).International journal of molecular medicine · 2025Review
- Bile acid accumulation induced by miR-122 deficiency in liver parenchyma promotes cancer cell growth in hepatocellular carcinoma.Molecular therapy. Nucleic acids · 2025Article
- Role of mitogens in normal and pathological liver regeneration.Hepatology communications · 2025Review
- Disrupting bile acid metabolism by suppressing Fxr causes hepatocellular carcinoma induced by YAP activation.Nature communications · 2025Article
- Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology.The American journal of pathology · 2025Review
- Gut Microbiota, Deranged Immunity, and Hepatocellular Carcinoma.Biomedicines · 2024Review
- The role of botanical triterpenoids and steroids in bile acid metabolism, transport, and signaling: Pharmacological and toxicological implications.Acta pharmaceutica Sinica. B · 2024Review
- Bile acids, gut microbiota, and therapeutic insights in hepatocellular carcinoma.Cancer biology & medicine · 2023Review
- Unveiling the complex relationship between gut microbiota and liver cancer: opportunities for novel therapeutic interventions.Gut microbes · 2023Review
- NOX as a Therapeutic Target in Liver Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Bile Acids-A Peek Into Their History and Signaling.Endocrinology · 2022Article
- Bile acids as drivers and biomarkers of hepatocellular carcinoma.World journal of hepatology · 2022Review
- Effects of intestine-specific deletion of fibroblast growth factor 15 on alcoholic liver disease development in mice.Liver research (Beijing, China) · 2022Article
- The role of bile acids in carcinogenesis.Cellular and molecular life sciences : CMLS · 2022Review
- Pleiotropic roles of FXR in liver and colorectal cancers.Molecular and cellular endocrinology · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
Farnesoid X receptor (FXR) belongs to the nuclear receptor superfamily with its endogenous ligands bile acids. Mice with whole body FXR deficiency develop liver tumors spontaneously, but the underlying mechanism is unclear. Moreover, it is unknown whether FXR deficiency in liver alone serves as a tumor initiator or promoter during liver carcinogenesis. This study aims to evaluate the effects of hepatocyte-specific FXR deficiency (FXR(hep-/-)) in liver tumor formation. The results showed that FXR(hep-/-) mice did not show spontaneous liver tumorigenesis with aging (up to 24 mo of age). Therefore FXR(hep-/-) mice were fed a bile acid (cholic acid)-containing diet alone or along with a liver tumor initiator, diethylnitrosamine (DEN). Thirty weeks later, no tumors were found in wild-type or FXR(hep-/-) mice without any treatment or with DEN only. However, with cholic acid, while only some wild-type mice developed tumors, all FXR(hep-/-) mice presented with severe liver injury and tumors. Interestingly, FXR(hep-/-) mouse livers increased basal expression of tumor suppressor p53 protein, apoptosis, and decreased basal cyclin D1 expression, which may prevent tumor development in FXR(hep-/-) mice. However, cholic acid feeding reversed these effects in FXR(hep-/-) mice, which is associated with an increased cyclin D1 and decreased cell cycle inhibitors. More in-depth analysis indicates that the increased in cell growth might result from disturbance of the MAPK and JAK/Stat3 signaling pathways. In conclusion, this study shows that hepatic FXR deficiency may only serve as a tumor initiator, and increased bile acids is required for tumor formation likely by promoting cell proliferation.
Indexed as
Identifiers
What OpenQuestion holds
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.