ArticleGastroenterology2010
Esophageal squamous cell dysplasia and delayed differentiation with deletion of krüppel-like factor 4 in murine esophagus.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 78 citations in OpenAlex.
- Krüppel-like factor 4 downregulation during esophageal cancer formation facilitates immune evasion and impairs immunotherapy.Signal transduction and targeted therapy · 2026Article
- Laser-induced skin microenvironment remodeling via exosomal CEBPA-mediated crosstalk between keratinocyte and fibroblast.Journal of nanobiotechnology · 2026Article
- Oesophageal Epithelial Cell-Intrinsic MHCII Regulates Food Antigen-Dependent Eosinophilic Esophagitis in an IFNγ-Dependent Manner.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2026Article
- Review
- Epithelial Ikkβ deletion modulates immune responses and the IFNγ/CXCL9 axis during early esophageal carcinogenesis.Carcinogenesis · 2025Article
- PPDPF promotes the progression of esophageal squamous cell carcinoma via c-Myc/CD24 axis.Journal for immunotherapy of cancer · 2025Article
- Esophageal epithelial Ikkβ deletion promotes eosinophilic esophagitis in experimental allergy mouse model.The Journal of allergy and clinical immunology · 2025Article
- Self-sustaining long-term 3D epithelioid cultures reveal drivers of clonal expansion in esophageal epithelium.Nature genetics · 2024Article
- Mouse models to explore the biological and organismic role of DNA polymerase beta.Environmental and molecular mutagenesis · 2024Review
- All-Trans Retinoic Acid Promotes a Tumor Suppressive OTUD6B-β-TrCP-SNAIL Axis in Esophageal Squamous Cell Carcinoma and Enhances Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- A Kaleidoscope of Keratin Gene Expression and the Mosaic of Its Regulatory Mechanisms.International journal of molecular sciences · 2023Review
- p53 mutation in normal esophagus promotes multiple stages of carcinogenesis but is constrained by clonal competition.Nature communications · 2022Article
- A biomechanical switch regulates the transition towards homeostasis in oesophageal epithelium.Nature cell biology · 2021Article
- The development and stem cells of the esophagus.Development (Cambridge, England) · 2021Review
- The Partial Role of KLF4 and KLF5 in Gastrointestinal Tumors.Gastroenterology research and practice · 2021Review
- Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types.International journal of molecular sciences · 2020Review
- ARID1A prevents squamous cell carcinoma initiation and chemoresistance by antagonizing pRb/E2F1/c-Myc-mediated cancer stemness.Cell death and differentiation · 2020Article
- ΔNp63 in squamous cell carcinoma: defining the oncogenic routes affecting epigenetic landscape and tumour microenvironment.Molecular oncology · 2019Review
- KLF4 activates NFκB signaling and esophageal epithelial inflammation via the Rho-related GTP-binding protein RHOF.PloS one · 2019Article
- Mouse Cre-LoxP system: general principles to determine tissue-specific roles of target genes.Laboratory animal research · 2018Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND &
aimsKrüppel-like factor 4 (Klf; previously known a gut-enriched Krüppel-like factor) is a DNA-binding transcriptional regulator highly expressed in skin and gastrointestinal epithelia, specifically in regions of cellular differentiation. Homozygous null mice for Klf4 die shortly after birth from skin defects, precluding their analysis at later stages. The aim of this study was to analyze the function of Klf4 in keratinocyte biology and epithelial homeostasis in the adult by focusing on the squamous lined esophagus.
methodsBy using the ED-L2 promoter of Epstein-Barr virus to drive Cre, we obtained tissue-specific ablation of Klf4 in the squamous epithelia of the tongue, esophagus, and forestomach.
resultsMice with loss of Klf4 in esophageal epithelia survived to adulthood, bypassing the early lethality. Tissue-specific Klf4 knockout mice had increased basal cell proliferation and a delay in cellular maturation; these mice developed epithelial hypertrophy and subsequent dysplasia by 6 months of age. Moreover, loss of Klf4 in vivo was associated with increased expression of the pro-proliferative Klf5, and Klf4 down-regulated Klf5 both transcriptionally and posttranscriptionally. By using gene expression profiling, we also showed decreased expression of critical late-stage differentiation factors and identified alterations of several genes important in cellular differentiation.
conclusionsKlf4 is essential for squamous epithelial differentiation in vivo and interacts with Klf5 to maintain normal epithelial homeostasis.
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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.