ArticleOncogene2020
Commonly observed RNF43 mutations retain functionality in attenuating Wnt/β-catenin signaling and unlikely confer Wnt-dependency onto colorectal cancers.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 49 citations in OpenAlex.
- RAS pathway mutations orchestrate chromatin reconfiguration and transcriptional rewiring in colorectal cancer.Cell communication and signaling : CCS · 2026Article
- Evolving patterns of co-mutations from tumor initiation to metastatic progression.Nature genetics · 2026Article
- Article
- Loss of ZNRF3/RNF43 unleashes EGFR in cancer.eLife · 2026Article
- BRAFiScience · 2025Article
- Clinical implications of Wnt pathway genetic alterations in men with advanced prostate cancer.Prostate cancer and prostatic diseases · 2025Article
- Lack of dominant-negative activity for tumor-related ZNRF3 missense mutations at endogenous levels.Oncogene · 2025Article
- 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
- Recurrent mutations in tumor suppressorScience advances · 2024Article
- Clinical and molecular characteristics ofTherapeutic advances in medical oncology · 2024Article
- Unraveling the impact of AXIN1 mutations on HCC development: Insights from CRISPR/Cas9 repaired AXIN1-mutant liver cancer cell lines.PloS one · 2024Article
- A New Wave of Targeting 'Undruggable' Wnt Signaling for Cancer Therapy: Challenges and Opportunities.Cells · 2023Review
- Somatic mutations can induce a noninflamed tumour microenvironment via their original gene functions, despite deriving neoantigens.British journal of cancer · 2023Article
- The Role of WNT Pathway Mutations in Cancer Development and an Overview of Therapeutic Options.Cells · 2023Review
- Article
- A Comprehensive Biomarker Analysis of Microsatellite Unstable/Mismatch Repair Deficient Colorectal Cancer Cohort Treated with Immunotherapy.International journal of molecular sciences · 2022Article
- Targeting ligand-dependent wnt pathway dysregulation in gastrointestinal cancers through porcupine inhibition.Pharmacology & therapeutics · 2022Review
- RNF43 G659fs is an oncogenic colorectal cancer mutation and sensitizes tumor cells to PI3K/mTOR inhibition.Nature communications · 2022Article
- Characterization of RNF43 frameshift mutations that drive Wnt ligand- and R-spondin-dependent colon cancer.The Journal of pathology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated RNF43 mutations lead to activation of β-catenin signaling through aberrantly increasing Wnt-receptor levels at the membrane. Importantly, inactivating RNF43 mutations have been suggested to render cancer cells sensitive to Wnt-based therapeutics. However, the extent to which RNF43 mutations lead to impaired regulation of Wnt/β-catenin signaling has been poorly investigated. Here, we observed that tumors with a functional mismatch repair system show a predominant 5'-location of truncating RNF43 mutations, suggesting C-terminal truncations such as the most commonly reported p.G659fs mutation, do not affect β-catenin signaling. In accordance, expressing C-terminal truncation mutants and wild-type RNF43, showed equal effects on β-catenin signaling, Wnt-receptor turnover, and DVL-binding. We confirmed these observations at endogenous levels by CRISPR-Cas9-mediated knockout of G659fs RNF43 expression in KM12 cells and generating comparable mutations in HEK293T cells. We could not confirm previous reports linking RNF43 to p53 and E-cadherin breakdown. Our data also suggest that only colorectal cancer cells harboring N-terminal mutations of RNF43 convey Wnt-dependency onto the tumor cells. Results of this study have potentially important clinical implications indicating that Wnt-based therapeutics should be applied cautiously in cancer patients harboring RNF43 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.