ArticleGastroenterology2010
Klf4 overexpression activates epithelial cytokines and inflammation-mediated esophageal squamous cell cancer in mice.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 67 citations in OpenAlex.
- HIF1α-KLF4 signaling dictates extra-erythrocyte expression of hemoglobin conferring sorafenib resistance in hepatocellular carcinoma.Signal transduction and targeted therapy · 2026Article
- Review
- Esophageal cancer: from pathogenesis to precision therapies.Signal transduction and targeted therapy · 2026Review
- TGF-β1/SMAD signaling downregulates KLF4 expression via direct transcriptional suppression and FAT10-mediated proteasomal degradation in hepatocellular carcinoma.Cell & bioscience · 2026Article
- KDM1A-driven RNF81 downregulation promotes gastric cancer progression via KLF4 destabilization.Oncogene · 2025Article
- Review
- The protective effect of iron isomaltoside on myocardial ischemia-reperfusion injury via the suppression of KLF4/NF-κB signaling.PloS one · 2025Article
- KLF4: a multifunctional nexus connecting tumor progression and immune regulation.Frontiers in immunology · 2025Review
- Transcriptomic Profiling of Primary Microglia: Effects of miR-19a-3p and miR-19b-3p on Microglia Activation.International journal of molecular sciences · 2024Article
- The Regenerative Microenvironment of the Tissue Engineering for Urethral Strictures.Stem cell reviews and reports · 2024Review
- Review
- IL-1β transgenic mouse model of inflammation driven esophageal and oral squamous cell carcinoma.Scientific reports · 2023Article
- KLF4 transcription factor in tumorigenesis.Cell death discovery · 2023Review
- Construction and Quantitative Evaluation of a Tissue-Specific Sleeping Beauty by EDL2-Specific Transposase Expression in Esophageal Squamous Carcinoma Cell Line KYSE-30.Molecular biotechnology · 2023Article
- miR-92a-3p promotes breast cancer proliferation by regulating the KLF2/BIRC5 axis.Thoracic cancer · 2022Article
- The prognostic role of combining Krüppel-like factor 4 score and grade of inflammation in a Norwegian cohort of oral tongue squamous cell carcinomas.European journal of oral sciences · 2022Article
- Agent Clustering Strategy Based on Metabolic Flux Distribution and Transcriptome Expression for Novel Drug Development.Biomedicines · 2021Article
- Palmitic acid up regulates Gal-3 and induces insulin resistance in macrophages by mediating the balance between KLF4 and NF-κB.Experimental and therapeutic medicine · 2021Article
- Comprehensive Analysis of E3 Ubiquitin Ligases Reveals Ring Finger Protein 223 as a Novel Oncogene Activated by KLF4 in Pancreatic Cancer.Frontiers in cell and developmental biology · 2021Article
- Reactivation of super-enhancers by KLF4 in human Head and Neck Squamous Cell Carcinoma.Oncogene · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsEsophageal squamous cell cancer accounts for more than 90% of cases of esophageal cancers. Its pathogenesis involves chronic epithelial irritation, although the factors involved in the inflammatory process and the mechanisms of carcinogenesis are unknown. We sought to develop a mouse model of this cancer.
methodsWe used the ED-L2 promoter of Epstein-Barr virus to overexpress the transcriptional regulator Krüppel-like factor 4 (Klf4) in esophageal epithelia of mice; we used mouse primary esophageal keratinocytes to examine the mechanisms by which KLF4 induces cytokine production.
resultsKLF4 was an epithelial-specific mediator of inflammation; we developed a new mouse model of esophageal squamous dysplasia and inflammation-mediated squamous cell cancer. KLF4 activated a number of proinflammatory cytokines, including TNF-α, CXCL5, G-CSF and IL-1α, within keratinocytes in an NF-κB-dependent manner. KLF4 was not detected in proliferating or cancer cells, indicating a non-cell autonomous effect of KLF4 on proliferation and carcinogenesis.
conclusionsKLF4 has distinct functions in carcinogenesis; upregulation of Klf4 specifically in esophageal epithelial cells induces inflammation. This mouse model might be used to determine the molecular mechanisms of esophageal squamous cell cancer and inflammation-mediated carcinogenesis.
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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.