ArticleNature communications2020
A phospho-switch controls RNF43-mediated degradation of Wnt receptors to suppress tumorigenesis.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 64 citations in OpenAlex.
- Construction of a risk model based on folate metabolism-related genes to predict prognosis and immunological characteristics of stomach adenocarcinoma.Discover oncology · 2026Article
- Loss of ZNRF3/RNF43 unleashes EGFR in cancer.eLife · 2026Article
- Class IIa HDACs forced degradation allows resensitization of oxaliplatin-resistant FBXW7-mutated colorectal cancer.Molecular oncology · 2026Article
- PRICKLE3 protects VANGL proteins from CK1-mediated phosphorylation and RNF43-mediated degradation.Communications biology · 2025Article
- WNK kinase regulates plasma membrane levels of the WNT inhibitor RNF43: A WNK-RNF43 circuit regulates WNT signal suppression.bioRxiv : the preprint server for biology · 2025Article
- LncRNA MIR503HG regulates NETs-mediated NLRP3 inflammasome activation and NSCLC metastasis by enhancing the ubiquitination of C/EBPβ.Clinical and translational medicine · 2025Article
- Mechanistic insights into Wnt-β-catenin pathway activation and signal transduction.Nature reviews. Molecular cell biology · 2025Review
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Lack of dominant-negative activity for tumor-related ZNRF3 missense mutations at endogenous levels.Oncogene · 2025Article
- Enhanced response to dabrafenib plus trametinib in a patient withFrontiers in oncology · 2025Article
- Characterization of Wnt Signaling Pathway Aberrations in Metastatic Prostate Cancer.Molecular cancer research : MCR · 2024Article
- E3 ligases RNF43 and ZNRF3 display differential specificity for endocytosis of Frizzled receptors.Life science alliance · 2024Article
- 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
- Diagnostic, prognostic, and therapeutic potential of exosomal microRNAs in renal cancer.Pharmacological reports : PR · 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
- Intestinal Paneth cell differentiation relies on asymmetric regulation of Wnt signaling by Daam1/2.Science advances · 2023Article
- Article
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Frequent mutation of the tumour suppressor RNF43 is observed in many cancers, particularly colon malignancies. RNF43, an E3 ubiquitin ligase, negatively regulates Wnt signalling by inducing degradation of the Wnt receptor Frizzled. In this study, we discover that RNF43 activity requires phosphorylation at a triplet of conserved serines. This phospho-regulation of RNF43 is required for zebrafish development and growth of mouse intestinal organoids. Cancer-associated mutations that abrogate RNF43 phosphorylation cooperate with active Ras to promote tumorigenesis by abolishing the inhibitory function of RNF43 in Wnt signalling while maintaining its inhibitory function in p53 signalling. Our data suggest that RNF43 mutations cooperate with KRAS mutations to promote multi-step tumorigenesis via the Wnt-Ras-p53 axis in human colon cancers. Lastly, phosphomimetic substitutions of the serine trio restored the tumour suppressive activity of extracellular oncogenic mutants. Therefore, harnessing phospho-regulation of RNF43 might be a potential therapeutic strategy for tumours with RNF43 mutations.
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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.