ArticleNature communications2015
Activating CAR and β-catenin induces uncontrolled liver growth and tumorigenesis.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.
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
49 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Meta-Analysis Reveals the Prognostic Relevance of Nuclear and Membrane-Associated Bile Acid Receptors in Gastric Cancer.Clinical and translational gastroenterology · 2021Pooled it
- Molecular Signaling Pathways, Regulatory and Coactivator Networks, and Emerging Mechanisms in Hepatocellular Carcinoma.Biomedicines · 2026Review
- Cytochrome P450 enzymes as modulators of oncogenic signaling via the Wnt/β-catenin signaling pathway.Archives of toxicology · 2026Review
- The origin of hepatocellular carcinoma depends on metabolic zonation.Science (New York, N.Y.) · 2026Article
- TMEM106C, BSG, COPE, CDCA8, KPNA2, LIG1, UQCRH, and CCT5: Predictive of Survival and Immunotherapy Resistance in Hepatocellular Carcinoma.Human mutation · 2026Article
- Apocynin ameliorates liver fibrosis events in vivo through modulation of oxidative stress, inflammatory, and apoptotic mediators.BMC pharmacology & toxicology · 2025Article
- Constitutive Androstane Receptor induces Ribonucleotide Reductase-M2 expression and maintains hepatocyte ploidy in mice.bioRxiv : the preprint server for biology · 2025Article
- Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology.The American journal of pathology · 2025Review
- Endonucleosis mediates internalization of cytoplasm into the nucleus.Nature communications · 2024Article
- Diindoles produced from commensal microbiota metabolites function as endogenous CAR/Nr1i3 ligands.Nature communications · 2024Article
- Increased genomic instability and reshaping of tissue microenvironment underlie oncogenic properties ofScience advances · 2024Article
- MIF is a critical regulator of mononuclear phagocytic infiltration in hepatocellular carcinoma.iScience · 2023Article
- Microbiota-mediated reactivation of triclosan oxidative metabolites in colon tissues.Journal of hazardous materials · 2023Article
- HCV Core protein represses DKK3 expression via epigenetic silencing and activates the Wnt/β-catenin signaling pathway during the progression of HCC.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Article
- Clinical Relevance of the Constitutive Androstane Receptor.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Lymphocyte-Specific Protein-1 Suppresses Xenobiotic-Induced Constitutive Androstane Receptor and Subsequent Yes-Associated Protein-Activated Hepatocyte Proliferation.The American journal of pathology · 2022Article
- Target Therapy for Hepatocellular Carcinoma: Beyond Receptor Tyrosine Kinase Inhibitors and Immune Checkpoint Inhibitors.Biology · 2022Review
- Application of humanized mice to toxicology studies: Evaluation of the human relevance of the mode of action for rodent liver tumor formation by activators of the constitutive androstane receptor (CAR).Journal of toxicologic pathology · 2021Article
- Yes-Associated Protein Is Crucial for Constitutive Androstane Receptor-Driven Hepatocyte Proliferation But Not for Induction of Drug Metabolism Genes in Mice.Hepatology (Baltimore, Md.) · 2021Article
- Mutations and mechanisms of WNT pathway tumour suppressors in cancer.Nature reviews. Cancer · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Aberrant β-catenin activation contributes to a third or more of human hepatocellular carcinoma (HCC), but β-catenin activation alone is not sufficient to induce liver cancer in mice. Differentiated hepatocytes proliferate upon acute activation of either β-catenin or the nuclear xenobiotic receptor CAR. These responses are strictly limited and are tightly linked, since β-catenin is activated in nearly all of the CAR-dependent tumours generated by the tumour promoter phenobarbital. Here, we show that full activation of β-catenin in the liver induces senescence and growth arrest, which is overcome by combined CAR activation, resulting in uncontrolled hepatocyte proliferation, hepatomegaly and rapid lethality despite maintenance of normal liver function. Combining CAR activation with limited β-catenin activation induces tumorigenesis, and the tumours share a conserved gene expression signature with β-catenin-positive human HCC. These results reveal an unexpected route for hepatocyte proliferation and define a murine model of hepatocarcinogenesis with direct relevance to human HCC.
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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.