ArticleJournal of hepatology2015
Complete response of Ctnnb1-mutated tumours to β-catenin suppression by locked nucleic acid antisense in a mouse hepatocarcinogenesis model.
Article in Journal of hepatology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- WNT-β-catenin signalling in hepatocellular carcinoma: from bench to clinical trials.Nature reviews. Gastroenterology & hepatology · 2026Review
- Chemoprevention of hepatocellular carcinoma using N-acetylgalactosamine-conjugated siRNAs.Disease models & mechanisms · 2025Article
- Precision targeting of β-catenin induces tumor reprogramming and immunity in hepatocellular cancers.Nature communications · 2025Article
- A lung cancer mouse model system based on an inbred C3H strain: Ultrasound imaging, pathological analysis, and proteomic biomarker identification.Veterinary world · 2025Article
- Hepatocellular carcinoma: signaling pathways and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Role of the Wnt/β-catenin signaling pathway in the development of HCC.Frontiers in immunology · 2025Review
- Wnt/β-Catenin Signaling in Liver Pathobiology.Annual review of pathology · 2025Review
- Wnt/β-catenin signaling pathway in liver biology and tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- Wnt/β-Catenin signaling pathway in hepatocellular carcinoma: pathogenic role and therapeutic target.Frontiers in oncology · 2024Review
- Comprehensive characterization of enhancer RNA in hepatocellular carcinoma reveals three immune subtypes with implications for immunotherapy.Molecular therapy oncolytics · 2022Article
- β-Catenin signaling in hepatocellular carcinoma.The Journal of clinical investigation · 2022Review
- Detection ofDiagnostics (Basel, Switzerland) · 2021Article
- Review
- An m6A-Related Prognostic Biomarker Associated With the Hepatocellular Carcinoma Immune Microenvironment.Frontiers in pharmacology · 2021Article
- Metabolism-associated molecular classification of hepatocellular carcinoma.Molecular oncology · 2020Article
- Article
- Targeting murine alveolar macrophages by the intratracheal administration of locked nucleic acid containing antisense oligonucleotides.Drug delivery · 2019Article
- Bromodomain and Extraterminal (BET) Proteins Regulate Hepatocyte Proliferation in Hepatocyte-Driven Liver Regeneration.The American journal of pathology · 2018Article
- Article
- Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology.Annual review of pathology · 2018Review
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9 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsHepatocellular cancer (HCC) remains a disease of poor prognosis, highlighting the relevance of elucidating key molecular aberrations that may be targeted for novel therapies. Wnt signalling activation, chiefly due to mutations in CTNNB1, have been identified in a major subset of HCC patients. While several in vitro proof of concept studies show the relevance of suppressing Wnt/β-catenin signalling in HCC cells or tumour xenograft models, no study has addressed the impact of β-catenin inhibition in a relevant murine HCC model driven by Ctnnb1 mutations.
methodsWe studied the in vivo impact of β-catenin suppression by locked nucleic acid (LNA) antisense treatment, after establishing Ctnnb1 mutation-driven HCC by diethylnitrosamine and phenobarbital (DEN/PB) administration.
resultsThe efficacy of LNA directed against β-catenin vs. scrambled on Wnt signalling was demonstrated in vitro in HCC cells and in vivo in normal mice. The DEN/PB model leads to HCC with Ctnnb1 mutations. A complete therapeutic response in the form of abrogation of HCC was observed after ten treatments of tumour-bearing mice with β-catenin LNA every 48h as compared to the scrambled control. A decrease in β-catenin activity, cell proliferation and increased cell death was evident after β-catenin suppression. No effect of β-catenin suppression was evident in non-Ctnnb1 mutated HCC, observed after DEN-only administration.
conclusionsThus, we provide the in vivo proof of concept that β-catenin suppression in HCC will be of significant therapeutic benefit, provided the tumours display Wnt activation via mechanisms like CTNNB1 mutations.
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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.