ArticleThe EMBO journal2020
RNF43 truncations trap CK1 to drive niche-independent self-renewal in cancer.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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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
30 citing papers in PubMed, 47 citations in OpenAlex.
- PRICKLE3 protects VANGL proteins from CK1-mediated phosphorylation and RNF43-mediated degradation.Communications biology · 2025Article
- 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
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Lack of dominant-negative activity for tumor-related ZNRF3 missense mutations at endogenous levels.Oncogene · 2025Article
- Wnt/β-catenin signaling pathway: proteins' roles in osteoporosis and cancer diseases and the regulatory effects of natural compounds on osteoporosis.Molecular medicine (Cambridge, Mass.) · 2024Review
- E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled receptors.Life science alliance · 2024Article
- Advancements in Research and Treatment Applications of Patient-Derived Tumor Organoids in Colorectal Cancer.Cancers · 2024Review
- New Target(s) for RNF43 Regulation: Implications for Therapeutic Strategies.International journal of molecular sciences · 2024Review
- New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- RNF43 Inactivation Enhances the B-RAF/MEK Signaling and Creates a Combinatory Therapeutic Target in Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Clinical and molecular characteristics ofTherapeutic advances in medical oncology · 2024Article
- RNF43 and ZNRF3 in Wnt Signaling - A Master Regulator at the Membrane.International journal of stem cells · 2023Review
- Targeting ligand-dependent wnt pathway dysregulation in gastrointestinal cancers through porcupine inhibition.Pharmacology & therapeutics · 2022Review
- Clone wars: From molecules to cell competition in intestinal stem cell homeostasis and disease.Experimental & molecular medicine · 2022Review
- RNF43 G659fs is an oncogenic colorectal cancer mutation and sensitizes tumor cells to PI3K/mTOR inhibition.Nature communications · 2022Article
- Molecular Landscape of Small Bowel Adenocarcinoma.Cancers · 2022Review
- Review
- RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impairing liver regeneration and altering the liver lipid metabolic ground-state.Nature communications · 2022Article
- A FZD7-specific Antibody-Drug Conjugate Induces Ovarian Tumor Regression in Preclinical Models.Molecular cancer therapeutics · 2022Article
- Receptor control by membrane-tethered ubiquitin ligases in development and tissue homeostasis.Current topics in developmental biology · 2022Article
Corrections and comments
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Wnt/β-catenin signaling is a primary pathway for stem cell maintenance during tissue renewal and a frequent target for mutations in cancer. Impaired Wnt receptor endocytosis due to loss of the ubiquitin ligase RNF43 gives rise to Wnt-hypersensitive tumors that are susceptible to anti-Wnt-based therapy. Contrary to this paradigm, we identify a class of RNF43 truncating cancer mutations that induce β-catenin-mediated transcription, despite exhibiting retained Wnt receptor downregulation. These mutations interfere with a ubiquitin-independent suppressor role of the RNF43 cytosolic tail that involves Casein kinase 1 (CK1) binding and phosphorylation. Mechanistically, truncated RNF43 variants trap CK1 at the plasma membrane, thereby preventing β-catenin turnover and propelling ligand-independent target gene transcription. Gene editing of human colon stem cells shows that RNF43 truncations cooperate with p53 loss to drive a niche-independent program for self-renewal and proliferation. Moreover, these RNF43 variants confer decreased sensitivity to anti-Wnt-based therapy. Our data demonstrate the relevance of studying patient-derived mutations for understanding disease mechanisms and improved applications of precision medicine.
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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 Socratic graph.