ArticleNature communications2022
RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 65 citations in OpenAlex.
- The landscape of plasma proteomic links to human organ imaging.Nature communications · 2026Article
- Wnt/β-catenin signaling in hepatocellular carcinoma: a key player in resistance to targeted and immunotherapies.Carcinogenesis · 2026Review
- Identification and prognostic analysis of genes related to CTNNB1 mutations in hepatocellular carcinoma.Biology direct · 2026Article
- Glucose restriction reprograms lipid metabolism and enhances immunotherapy through ZNRF3-Wnt-SCD signaling axis.Journal for immunotherapy of cancer · 2026Article
- [Research advances on hepatocyte zonal changes in metabolic associated fatty liver disease].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Loss of ZNRF3/RNF43 unleashes EGFR in cancer.eLife · 2026Article
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Interpretable machine learning-based survival prediction and key gene identification in cancer using gene expression and clinical data.Translational cancer research · 2026Article
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- Advances in liver and pancreas organoids: how far we have come and where we go next.Nature reviews. Gastroenterology & hepatology · 2026Review
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- Targeted protein degradation of Wnt/β-catenin signaling pathway: an effective strategy for cancer therapy.Journal of translational medicine · 2025Review
- Lipid metabolism in cancer cells: Its role in hepatocellular carcinoma progression and therapeutic resistance.Hepatology communications · 2025Review
- Monod: model-based discovery and integration through fitting stochastic transcriptional dynamics to single-cell sequencing data.Nature methods · 2025Article
- Evaluation of genetic diversity and selection signals in gayal populations across four countries through whole-genome resequencing.Stress biology · 2025Article
- ZNRF3 in neurodevelopmental disorders: insights into Wnt signaling and therapeutic potential.Neurogenetics · 2025Review
- A germline variant of ring finger protein 43 in an early onset, treatment-resistant metastatic gastric cancer: a case report.Journal of gastrointestinal oncology · 2025Article
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
RNF43/ZNRF3 negatively regulate WNT signalling. Both genes are mutated in several types of cancers, however, their contribution to liver disease is unknown. Here we describe that hepatocyte-specific loss of Rnf43/Znrf3 results in steatohepatitis and in increase in unsaturated lipids, in the absence of dietary fat supplementation. Upon injury, Rnf43/Znrf3 deletion results in defective hepatocyte regeneration and liver cancer, caused by an imbalance between differentiation/proliferation. Using hepatocyte-, hepatoblast- and ductal cell-derived organoids we demonstrate that the differentiation defects and lipid alterations are, in part, cell-autonomous. Interestingly, ZNRF3 mutant liver cancer patients present poorer prognosis, altered hepatic lipid metabolism and steatohepatitis/NASH signatures. Our results imply that RNF43/ZNRF3 predispose to liver cancer by controlling the proliferative/differentiation and lipid metabolic state of hepatocytes. Both mechanisms combined facilitate the progression towards malignancy. Our findings might aid on the management of those RNF43/ZNRF3 mutated individuals at risk of developing fatty liver and/or liver cancer.
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