ArticleJournal of hepatology2012
Deletion of IFNγ enhances hepatocarcinogenesis in FXR knockout mice.
Article in Journal of hepatology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- A Narrative Review: Immunometabolic Interactions of Host-Gut Microbiota and Botanical Active Ingredients in Gastrointestinal Cancers.International journal of molecular sciences · 2024Review
- Interpretation of Farnesoid X Receptor Immunohistochemical Expression in Discriminating Hepatocellular Carcinoma from Its Non-Neoplastic Mimics as an Adjunct to Glypican 3.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Pleiotropic roles of FXR in liver and colorectal cancers.Molecular and cellular endocrinology · 2022Article
- Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer.Molecular biomedicine · 2021Review
- Farnesoid X receptor via Notch1 directs asymmetric cell division of Sox9Stem cell research & therapy · 2021Article
- Norcholic Acid Promotes Tumor Progression and Immune Escape by Regulating Farnesoid X Receptor in Hepatocellular Carcinoma.Frontiers in oncology · 2021Article
- Role of Farnesoid X Receptor and Bile Acids in Hepatic Tumor Development.Hepatology communications · 2018Article
- Update on FXR Biology: Promising Therapeutic Target?International journal of molecular sciences · 2018Review
- Long non-coding RNA00364 represses hepatocellular carcinoma cell proliferation via modulating p-STAT3-IFIT2 signaling axis.Oncotarget · 2017Article
- Article
- T lymphocyte SHP2-deficiency triggers anti-tumor immunity to inhibit colitis-associated cancer in mice.Oncotarget · 2017Article
- FXR induces SOCS3 and suppresses hepatocellular carcinoma.Oncotarget · 2015Article
- FXR and liver carcinogenesis.Acta pharmacologica Sinica · 2015Review
- STAT3 in hepatocellular carcinoma: new perspectives.Hepatic oncology · 2014Review
- Mechanisms of STAT3 activation in the liver of FXR knockout mice.American journal of physiology. Gastrointestinal and liver physiology · 2013Article
- Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice.Toxicology and applied pharmacology · 2013Article
- Bile Acid Receptors and Liver Cancer.Current pathobiology reports · 2013Article
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsLiver tumor, especially hepatocellular carcinoma (HCC), is closely associated with chronic inflammation. We previously showed that farnesoid X receptor knockout (FXR(-)(/)(-)) mice displayed chronic inflammation and developed spontaneous liver tumors when they aged. However, the mechanism by which inflammation leads to HCC in the absence of FXR is unclear. Because IFNγ is one of the most upregulated pro-inflammatory cytokines in FXR(-)(/)(-) livers, we generated IFNγ(-)(/)(-)FXR(-)(/)(-) double knockout mice to determine IFNγ's roles in hepatocarcinogenesis.
methodsIFNγ(-)(/)(-) mice were crossed with an FXR(-)(/)(-) C57BL/6 background or injected i.p. with the hepatocarcinogen diethylnitrosamine (DEN). Hepatocarcinogenesis was analyzed with biochemical and histological methods.
resultsIFNγ deletion accelerated spontaneous hepatocarcinogenesis in FXR(-)(/)(-) mice and increased the susceptibility to DEN-induced hepatocarcinogenesis. IFNγ deletion enhanced activation of HCC promoters STAT3 and JNK/c-Jun, but abolished induction of p53 in IFNγ(-)(/)(-) livers after acute DEN-induced injury. Furthermore, hepatic p53 expression increased in aged wild type mice but not in aged IFNγ(-)(/)(-) and IFNγ(-)(/)(-)FXR(-)(/)(-) mice, while activation of STAT3 and JNK/c-Jun was enhanced in aged IFNγ(-)(/)(-) and IFNγ(-)(/)(-)FXR(-)(/)(-) mice. In addition, IFNγ inhibited liver cancer xenograft growth and impaired IL-6-induced STAT3 phosphorylation by inducing SOCS1/3 expression.
conclusionsIncreased IFNγ expression in FXR(-)(/)(-) livers represents a protective response of the liver against chronic injury and tumorigenesis. IFNγ suppresses hepatocarcinogenesis by inducing p53 expression and preventing STAT3 activation.
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