ArticlePLoS genetics2015
Identification of Chemical Inhibitors of β-Catenin-Driven Liver Tumorigenesis in Zebrafish.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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.
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Who cites it
48 citing papers in PubMed, 81 citations in OpenAlex.
- MicroRNA-21 promotes dysregulated lipid metabolism and hepatocellular carcinoma.Disease models & mechanisms · 2026Article
- Mechanistic Insights and Clinical Implications of ELK1 in Solid Tumors: A Narrative Review.Cells · 2025Review
- The Antidepressant Drug Amitriptyline Affects Human SH-SY5Y Neuroblastoma Cell Proliferation and Modulates Autophagy.International journal of molecular sciences · 2024Article
- Phospholipid isotope tracing suggests β-catenin-driven suppression of phosphatidylcholine metabolism in hepatocellular carcinoma.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2024Article
- Zebrafish live imaging: a strong weapon in anticancer drug discovery and development.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- The janus face of serotonin: Regenerative promoter and chronic liver disease aggravator.Heliyon · 2024Review
- DNA hypomethylation activates Cdk4/6 and Atr to induce DNA replication and cell cycle arrest to constrain liver outgrowth in zebrafish.Nucleic acids research · 2024Article
- Inhibitory Effect of Acetaminophen on Ocular Pigmentation and its Relationship with Thyroxine in Zebrafish Embryos.Bulletin of environmental contamination and toxicology · 2024Article
- Methods to Study Liver Disease Using Zebrafish Larvae.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Using different zebrafish models to explore liver regeneration.Frontiers in cell and developmental biology · 2024Review
- Phospholipid isotope tracing reveals β-catenin-driven suppression of phosphatidylcholine metabolism in hepatocellular carcinoma.bioRxiv : the preprint server for biology · 2023Article
- Review
- Update on Hepatobiliary Plasticity.Seminars in liver disease · 2023Article
- Repurposing Antidepressants and Phenothiazine Antipsychotics as Efflux Pump Inhibitors in Cancer and Infectious Diseases.Antibiotics (Basel, Switzerland) · 2023Review
- p53-Bad* Fusion Gene Therapy Induces Apoptosis In Vitro and Reduces Zebrafish Tumor Burden in Hepatocellular Carcinoma.Molecular pharmaceutics · 2023Article
- Zebrafish Models of Paediatric Brain Tumours.International journal of molecular sciences · 2022Review
- Review
- What Zebrafish and Nanotechnology Can Offer for Cancer Treatments in the Age of Personalized Medicine.Cancers · 2022Review
- Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) is one of the most lethal human cancers. The search for targeted treatments has been hampered by the lack of relevant animal models for the genetically diverse subsets of HCC, including the 20-40% of HCCs that are defined by activating mutations in the gene encoding β-catenin. To address this chemotherapeutic challenge, we created and characterized transgenic zebrafish expressing hepatocyte-specific activated β-catenin. By 2 months post fertilization (mpf), 33% of transgenic zebrafish developed HCC in their livers, and 78% and 80% of transgenic zebrafish showed HCC at 6 and 12 mpf, respectively. As expected for a malignant process, transgenic zebrafish showed significantly decreased mean adult survival compared to non-transgenic control siblings. Using this novel transgenic model, we screened for druggable pathways that mediate β-catenin-induced liver growth and identified two c-Jun N-terminal kinase (JNK) inhibitors and two antidepressants (one tricyclic antidepressant, amitriptyline, and one selective serotonin reuptake inhibitor) that suppressed this phenotype. We further found that activated β-catenin was associated with JNK pathway hyperactivation in zebrafish and in human HCC. In zebrafish larvae, JNK inhibition decreased liver size specifically in the presence of activated β-catenin. The β-catenin-specific growth-inhibitory effect of targeting JNK was conserved in human liver cancer cells. Our other class of hits, antidepressants, has been used in patient treatment for decades, raising the exciting possibility that these drugs could potentially be repurposed for cancer treatment. In support of this proposal, we found that amitriptyline decreased tumor burden in a mouse HCC model. Our studies implicate JNK inhibitors and antidepressants as potential therapeutics for β-catenin-induced liver tumors.
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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.