ArticleGut2014
Investigation of the atypical FBXW7 mutation spectrum in human tumours by conditional expression of a heterozygous propellor tip missense allele in the mouse intestines.
Article in Gut, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- FBXW7 Gene Mutation and Expression in Colorectal Cancer (CRC): A Systematic Review from Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2025Pooled it
- Comprehensive Molecular Characterization of High-Grade Endometrial Cancer in an Ancestrally Diverse Cohort.bioRxiv : the preprint server for biology · 2026Article
- Molecular insights and clinical implications for the tumor suppressor role of SCFBiochimica et biophysica acta. Reviews on cancer · 2024Review
- Functional analysis reveals driver cooperativity and novel mechanisms in endometrial carcinogenesis.EMBO molecular medicine · 2023Article
- FBXW7 in breast cancer: mechanism of action and therapeutic potential.Journal of experimental & clinical cancer research : CR · 2023Review
- The Role of FBXW7 in Gynecologic Malignancies.Cells · 2023Review
- Review
- Systematic Discovery of FBXW7-Binding Phosphodegrons Highlights Mitogen-Activated Protein Kinases as Important Regulators of Intracellular Protein Levels.International journal of molecular sciences · 2022Article
- Anti-miR-135/SPOCK1 axis antagonizes the influence of metabolism on drug response in intestinal/colon tumour organoids.Oncogenesis · 2022Article
- FBW7 suppresses ovarian cancer development by targeting the NMolecular cancer · 2021Article
- Article
- Autophagy Regulates VDAC3 Ubiquitination by FBXW7 to Promote Erastin-Induced Ferroptosis in Acute Lymphoblastic Leukemia.Frontiers in cell and developmental biology · 2021Article
- Mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon: detailed molecular characterisation of two cases indicates a distinct colorectal cancer entity.The journal of pathology. Clinical research · 2021Article
- Article
- Function and regulation of F-box/WD repeat-containing protein 7.Oncology letters · 2020Review
- Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- The WD40 domain of FBXW7 is a poly(ADP-ribose)-binding domain that mediates the early DNA damage response.Nucleic acids research · 2019Article
- FBXW7 in Cancer: What Has Been Unraveled Thus Far?Cancers · 2019Review
- An FBXW7-ZEB2 axis links EMT and tumour microenvironment to promote colorectal cancer stem cells and chemoresistance.Oncogenesis · 2019Article
- The deubiquitinase USP9X regulates FBW7 stability and suppresses colorectal cancer.The Journal of clinical investigation · 2018Article
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4 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveFBXW7 encodes the substrate recognition component of a ubiquitin ligase that degrades targets such as Notch1, c-Jun, c-Myc and cyclin E. FBXW7 mutations occur in several tumour types, including colorectal cancers. The FBXW7 mutation spectrum in cancers is unusual. Some tumours have biallelic loss of function mutations but most have monoallelic missense mutations involving specific arginine residues at β-propellor tips involved in substrate recognition.
designFBXW7 functional studies have generally used null systems. In order to analyse the most common mutations in human tumours, we created a Fbxw7(fl(R482Q))(/+) mouse and conditionally expressed this mutation in the intestines using Vill-Cre. We compared these mice with heterozygous null (Fbxw7(+/-)) mutants.
resultsA few sizeable intestinal adenomas occurred in approximately 30% of R482Q/+ and Fbxw7(+/-) mice at age >300 days. Breeding the R482Q allele onto Apc mutant backgrounds led to accelerated morbidity and increased polyp numbers and size. Within the small bowel, polyp distribution was shifted proximally. Elevated levels of two particular Fbxw7 substrates, Klf5 and Tgif1, were found in normal intestine and adenomas of R482Q/+, R482Q/R482Q and Fbxw7(-/-) mice, but not Fbxw7(+/-) animals. On the Apc mutant background, Fbxw7(+/-) mutants had a phenotype intermediate between Fbxw7 wild-type and R482Q/+ mice.
conclusionsHeterozygous Fbxw7 propellor tip (R482Q) mutations promote intestinal tumorigenesis on an Apc mutant background. Klf5 and Tgif1 are strong candidates for mediating this effect. Although heterozygous null Fbxw7 mutations also promote tumour growth, these have a weaker effect than R482Q. These findings explain the FBXW7 mutation spectrum found in human cancers, and emphasise the need for animal models faithfully to reflect human disease.
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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.