ArticleCancer biology & therapy2016
KLF4 is downregulated but not mutated during human esophageal squamous cell carcinogenesis and has tumor stage-specific functions.
Article in Cancer biology & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- A comprehensive analysis of mRNA expression profiles of Esophageal Squamous Cell Carcinoma reveals downregulation of Desmoglein 1 and crucial genomic targets.Cancer biomarkers : section A of Disease markers · 2023Pooled it
- KLF family of proteins in gastrointestinal tumors (Review).Oncology letters · 2026Review
- Spatial omics study reveals molecular-cellular dynamics of tumor ecosystem in esophageal squamous-cell carcinoma initiation and progression.Cell reports. Medicine · 2026Article
- Review
- GABRP inhibits the progression of oesophageal cancer by regulating CFTR: Integrating bioinformatics analysis and experimental validation.International journal of experimental pathology · 2024Article
- KLF4 is an epigenetically modulated, context-dependent tumor suppressor.Frontiers in cell and developmental biology · 2024Review
- Self-Renewal and Pluripotency in Osteosarcoma Stem Cells' Chemoresistance: Notch, Hedgehog, and Wnt/β-Catenin Interplay with Embryonic Markers.International journal of molecular sciences · 2023Review
- New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.Seminars in cancer biology · 2023Review
- KLF4 transcription factor in tumorigenesis.Cell death discovery · 2023Review
- Article
- The Effect of Organoselenium Compounds on Histone Deacetylase Inhibition and Their Potential for Cancer Therapy.International journal of molecular sciences · 2021Review
- Reciprocal regulation of integrin β4 and KLF4 promotes gliomagenesis through maintaining cancer stem cell traits.Journal of experimental & clinical cancer research : CR · 2019Article
- Overexpression of Krüppel-Like Factor 4 Suppresses Migration and Invasion of Non-Small Cell Lung Cancer Through c-Jun-NH2-Terminal Kinase/Epithelial-Mesenchymal Transition Signaling Pathway.Frontiers in pharmacology · 2019Article
- Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients.Gastroenterology · 2018Review
- Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma.Nature communications · 2017Article
- Novel tumor-suppressor function of KLF4 in pediatric T-cell acute lymphoblastic leukemia.Experimental hematology · 2017Review
- Krüppel-Like Factor 4 Enhances Sensitivity of Cisplatin to Esophageal Squamous Cell Carcinoma (ESCC) Cells.Medical science monitor : international medical journal of experimental and clinical research · 2017Article
- KLF4 is regulated by RAS/RAF/MEK/ERK signaling through E2F1 and promotes melanoma cell growth.Oncogene · 2017Article
- SP and KLF Transcription Factors in Digestive Physiology and Diseases.Gastroenterology · 2017Review
- Restoration of KLF4 Inhibits Invasion and Metastases of Lung Adenocarcinoma through Suppressing MMP2.Journal of Cancer · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The transcriptional regulator Krüppel-like factor 4 (KLF4) is decreased in human esophageal squamous cell cancer (ESCC), and Klf4 deletion in mice produces squamous cell dysplasia. Nonetheless the mechanisms of KLF4 downregulation in ESCC and the functions of KLF4 during ESCC development and progression are not well understood. Here, we sought to define the regulation of KLF4 and delineate the stage-specific effects of KLF4 in ESCC. We found that KLF4 expression was decreased in human ESCC and in 8 of 9 human ESCC cell lines. However, by genomic sequencing, we observed no KLF4 mutations or copy number changes in any of 52 human ESCC, suggesting other mechanisms for KLF4 silencing. In fact, KLF4 expression in human ESCC cell lines was increased by the DNA methylation inhibitor 5-azacytidine, suggesting an epigenetic mechanism for KLF4 silencing. Surprisingly, while KLF4 decreased in high-grade dysplasia and early stage tumors, KLF4 increased with advanced cancer stage, and KLF4 expression in ESCC was inversely correlated with survival. Interestingly, KLF4 promoted invasion of human ESCC cells, providing a functional link to the stage-specific expression of KLF4. Taken together, these findings suggest that KLF4 loss is necessary for esophageal tumorigenesis but that restored KLF4 expression in ESCC promotes tumor spread. Thus, the use of KLF4 as a diagnostic and therapeutic target in cancer requires careful consideration of context.
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