ArticleOncotarget2016
RNF43 and ZNRF3 are commonly altered in serrated pathway colorectal tumorigenesis.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- GenoGlyph: Pan-cancer genomic mutation inference and risk stratification from diagnostic histopathology slides.Research square · 2026Article
- Article
- Article
- Do all colorectal mucinous adenocarcinomas arise via the serrated neoplasia pathway?The journal of pathology. Clinical research · 2026Article
- Loss of ZNRF3/RNF43 unleashes EGFR in cancer.eLife · 2026Article
- Machine Learning Algorithm for the Detection of Tumor Microsatellite Instability Based on Multiomics Biomarkers.JCO clinical cancer informatics · 2026Article
- Targeting β-catenin: PROTACs and precision degraders for Wnt-driven cancers.Frontiers in oncology · 2026Review
- A set cover algorithm identifies minimal circulating tumour DNA sequencing targets for colorectal cancer detection.Scientific reports · 2025Article
- Transcriptional patterns of cancer-related genes in primary and metastatic tumours revealed by machine learning.BMC biology · 2025Article
- BRAFiScience · 2025Article
- Tenascin-C Potentiates Wnt Signaling in Thyroid Cancer.Endocrinology · 2025Article
- Combinatorial In Vivo Genome Editing Identifies Widespread Epistasis and an Accessible Fitness Landscape During Lung Tumorigenesis.Molecular biology and evolution · 2025Article
- Exploring WNT pathway dysregulation in serrated colorectal cancer for improved diagnostic and therapeutic strategies.Frontiers in genetics · 2025Article
- Zinc and its binding proteins: essential roles and therapeutic potential.Archives of toxicology · 2025Review
- Deleterious ZNRF3 germline variants cause neurodevelopmental disorders with mirror brain phenotypes via domain-specific effects on Wnt/β-catenin signaling.American journal of human genetics · 2024Article
- New insights in ubiquitin-dependent Wnt receptor regulation in tumorigenesis.In vitro cellular & developmental biology. Animal · 2024Review
- Aberrant PRDM2 methylation as an early event in serrated lesions destined to evolve into microsatellite-instable colorectal cancers.The journal of pathology. Clinical research · 2024Article
- Inherited BRCA1 and RNF43 pathogenic variants in a familial colorectal cancer type X family.Familial cancer · 2024Article
- Wnt Signaling and Therapeutic Resistance in Castration-Resistant Prostate Cancer.Current pharmacology reports · 2023Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serrated pathway colorectal cancers (CRCs) are characterised by a BRAF mutation and half display microsatellite instability (MSI). The Wnt pathway is commonly upregulated in conventional CRC through APC mutation. By contrast, serrated cancers do not mutate APC. We investigated mutation of the ubiquitin ligases RNF43 and ZNRF3 as alternate mechanism of altering the Wnt signal in serrated colorectal neoplasia. RNF43 was mutated in 47/54(87%) BRAF mutant/MSI and 8/33(24%) BRAF mutant/microsatellite stable cancers compared to only 3/79(4%) BRAF wildtype cancers (p<0.0001). ZNRF3 was mutated in 16/54(30%) BRAF mutant/MSI and 5/33(15%) BRAF mutant/microsatellite stable compared to 0/27 BRAF wild type cancers (p=0.004). An RNF43 frameshift mutation (X659fs) occurred in 80% BRAF mutant/MSI cancers. This high rate was verified in a second series of 25/35(71%) BRAF mutant/MSI cancers. RNF43 and ZNRF3 had lower transcript expression in BRAF mutant compared to BRAF wildtype cancers and less cytoplasmic protein expression in BRAF mutant/MSI compared to other subtypes. Treatment with a porcupine inhibitor reduced RNF43/ZNRF3 mutant colony growth by 50% and synergised with a MEK inhibitor to dramatically reduce growth. This study suggests inactivation of RNF43 and ZNRF3 is important in serrated tumorigenesis and has identified a potential therapeutic strategy for this cancer subtype.
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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.