ArticleCell death and differentiation2016
KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer.
Article in Cell death and differentiation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 82 citations in OpenAlex.
- Krüppel-like factor 4 downregulation during esophageal cancer formation facilitates immune evasion and impairs immunotherapy.Signal transduction and targeted therapy · 2026Article
- Andrographolide Alleviates Liver Damage Caused byMicroorganisms · 2026Article
- Krüppel-Like Factor 4, a Hub Gate for Cell Crosstalk in Tumor Microenvironment.Cancer medicine · 2026Review
- Epithelial zinc finger protein in lung adenocarcinoma: prognostic biomarker with molecular and clinical implications.Hereditas · 2025Article
- Construction and clinical significance of prognostic risk markers based on cancer driver genes in lung adenocarcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- KLF4 enhances transplantation-induced hematopoiesis by inhibiting TLRs and noncanonical NFκB signaling at a steady state.Experimental hematology · 2025Article
- KLF4: a multifunctional nexus connecting tumor progression and immune regulation.Frontiers in immunology · 2025Review
- The reprogramming factor KLF4 in normal and malignant blood cells.Frontiers in immunology · 2025Review
- Gene expression profiling, prognosis, and immune microenvironment of KLF4 in malignancies.PloS one · 2025Article
- Inhibition of lung tumorigenesis by transient reprogramming in cancer cells.Cell death & disease · 2024Article
- Krüppel-like factors: potential roles in blood-brain barrier dysfunction and epileptogenesis.Acta pharmacologica Sinica · 2024Review
- A risk score based on polyamine metabolism and chemotherapy-related genes predicts prognosis and immune cells infiltration of lung adenocarcinoma.Journal of cellular and molecular medicine · 2024Article
- Article
- Chromatin modifiers in human disease: from functional roles to regulatory mechanisms.Molecular biomedicine · 2024Review
- KLF4 is an epigenetically modulated, context-dependent tumor suppressor.Frontiers in cell and developmental biology · 2024Review
- SilenceREIN: seeking silencers on anchors of chromatin loops by deep graph neural networks.Briefings in bioinformatics · 2023Article
- Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer.Molecular cancer · 2023Review
- MED27 plays a tumor-promoting role in breast cancer progression by targeting KLF4.Cancer science · 2023Article
- KLF4 transcription factor in tumorigenesis.Cell death discovery · 2023Review
- Lung Cancer Gene Regulatory Network of Transcription Factors Related to the Hallmarks of Cancer.Current issues in molecular biology · 2023Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Lung cancer is the leading cause of cancer-related mortality in both men and women worldwide. To identify novel factors that contribute to lung cancer pathogenesis, we analyzed a lung cancer database from The Cancer Genome Atlas and found that Krüppel-like Factor 4 (KLF4) expression is significantly lower in patients' lung cancer tissue than in normal lung tissue. In addition, we identified seven missense mutations in the KLF4 gene. KLF4 is a transcription factor that regulates cell proliferation and differentiation as well as the self-renewal of stem cells. To understand the role of KLF4 in the lung, we generated a tamoxifen-induced Klf4 knockout mouse model. We found that KLF4 inhibits lung cancer cell growth and that depletion of Klf4 altered the differentiation pattern in the developing lung. To understand how KLF4 functions during lung tumorigenesis, we generated the K-ras(LSL-G12D/+);Klf4(fl/fl) mouse model, and we used adenovirus-expressed Cre to induce K-ras activation and Klf4 depletion in the lung. Although Klf4 deletion alone or K-ras mutation alone can trigger lung tumor formation, Klf4 deletion combined with K-ras mutation significantly enhanced lung tumor formation. We also found that Klf4 deletion in conjunction with K-ras activation caused lung inflammation. To understand the mechanism whereby KLF4 is regulated during lung tumorigenesis, we analyzed KLF4 promoter methylation and the profiles of epigenetic factors. We found that Class I histone deacetylases (HDACs) are overexpressed in lung cancer and that HDAC inhibitors induced expression of KLF4 and inhibited proliferation of lung cancer cells, suggesting that KLF4 is probably repressed by histone acetylation and that HDACs are valuable drug targets for lung cancer treatment.
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