ArticleOncotarget2017
Fbxw7 haploinsufficiency loses its protection against DNA damage and accelerates MNU-induced gastric carcinogenesis.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- FBXW7 in gastrointestinal cancers: from molecular mechanisms to therapeutic prospects.Frontiers in pharmacology · 2024Review
- Different miRNAs Related toInternational journal of molecular sciences · 2023Article
- The immune microenvironment in gastric adenocarcinoma.Nature reviews. Gastroenterology & hepatology · 2022Review
- Overexpression of F-box and WD repeat domain containing 7 prevents tumor growth of bladder cancer cells through regulating SREBP1a.Translational andrology and urology · 2022Article
- Tumor Suppressor FBXW7 and Its Regulation of DNA Damage Response and Repair.Frontiers in cell and developmental biology · 2021Review
- Cancer Explant Models.Current topics in microbiology and immunology · 2021Article
- Transcriptomic and Genomic Testing to Guide Individualized Treatment in Chemoresistant Gastric Cancer Case.Biomedicines · 2020Article
- Urine metabolomics of rats with chronic atrophic gastritis.PloS one · 2020Article
- 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
- Inhibition of Bcl6b promotes gastric cancer by amplifying inflammation in mice.Cell communication and signaling : CCS · 2019Article
- Molecular carcinogenesis of gastric cancer: Lauren classification, mucin phenotype expression, and cancer stem cells.International journal of clinical oncology · 2019Review
- F-box/WD-40 repeat-containing protein 7: A potential target in the progression and treatment of gastrointestinal malignancy.Oncology letters · 2019Review
- FBXW7 in Cancer: What Has Been Unraveled Thus Far?Cancers · 2019Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fbxw7, a subunit of the SCF E3 ubiquitin ligase, recognizes oncoprotein substrates and leads to their proteasomal degradation. Fbxw7 acts as a tumor suppressor via inducing apoptosis and growth arrest in various kinds of tumors. To clarify the initiating role in gastric carcinogenesis as well as the histologic characterization of tumor in Fbxw7 allele haploinsufficient mice, we generated Fbxw7 heterozygous knockout mice (Fbxw7+/-) and treated them with chemical carcinogen N-methyl-N-nitrosourea (MNU) at 5-6 weeks of age. We also treated mouse embryo fibroblasts (MEFs) from Fbxw7+/- and Fbxw7+/+ mice with MNU and examined cell DNA damage via comet assay. The protein expression of Fbxw7 and its substrate c-Myc from mouse tumors, as well as human tumors sampled from six patients, were detected by Western blot. As results, the tumor incidence was obviously higher in Fbxw7+/- mice (13/20) than in Fbxw7+/+ mice (6/20) after 35-week observation. Intestinal metaplasia (P = 0.013) and dysplasia (P = 0.036) were more severe in Fbxw7+/- mice than in Fbxw7+/+ mice. The repair potential of DNA damage was suppressed in MEFs from Fbxw7+/- mice after MNU exposure. Increased c-Myc expression was accompanied by decreased Fbxw7 protein expression in tumor tissues from mouse and patients. In conclusion, Fbxw7 haploinsufficiency increased the risk of gastric carcinogenesis induced by MNU, which is associated with the accumulation of DNA damage as well as c-Myc oncoprotein.
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