ArticleCells2020
KLF4 Acts as a wt-CFTR Suppressor through an AKT-Mediated Pathway.
Article in Cells, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Revealing the impact ofFrontiers in immunology · 2025Article
- Ovarian Tumor Domain-Containing 7B Attenuates Pathological Cardiac Hypertrophy by Inhibiting Ubiquitination and Degradation of Krüppel-Like Factor 4.Journal of the American Heart Association · 2023Article
- Transcriptional Regulation of Airway Epithelial Cell Differentiation: Insights into the Notch Pathway and Beyond.International journal of molecular sciences · 2023Review
- Lung Cancer Gene Regulatory Network of Transcription Factors Related to the Hallmarks of Cancer.Current issues in molecular biology · 2023Article
- Krüppel-Like Factor 5 Regulates CFTR Expression Through Repression by Maintaining Chromatin Architecture Coupled with Direct Enhancer Activation.Journal of molecular biology · 2022Article
- CFTR and Gastrointestinal Cancers: An Update.Journal of personalized medicine · 2022Review
- Article
- Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis.Pathophysiology : the official journal of the International Society for Pathophysiology · 2021Review
- Epithelial Barrier Dysfunction in Chronic Respiratory Diseases.Frontiers in physiology · 2021Review
- Mutant CFTR Drives TWIST1 mediated epithelial-mesenchymal transition.Cell death & disease · 2020Article
- Impact of KLF4 on Cell Proliferation and Epithelial Differentiation in the Context of Cystic Fibrosis.International journal of molecular sciences · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cystic Fibrosis (CF) is caused by >2000 mutations in the CF transmembrane conductance regulator (CFTR) gene, but one mutation-F508del-occurs in ~80% of patients worldwide. Besides its main function as an anion channel, the CFTR protein has been implicated in epithelial differentiation, tissue regeneration, and, when dysfunctional, cancer. However, the mechanisms that regulate such relationships are not fully elucidated. Krüppel-like factors (KLFs) are a family of transcription factors (TFs) playing central roles in development, stem cell differentiation, and proliferation. Herein, we hypothesized that these TFs might have an impact on CFTR expression and function, being its missing link to differentiation. Our results indicate that KLF4 (but not KLF2 nor KLF5) is upregulated in CF vs. non-CF cells and that it negatively regulates wt-CFTR expression and function. Of note, F508del-CFTR expressing cells are insensitive to KLF4 modulation. Next, we investigated which KLF4-related pathways have an effect on CFTR. Our data also show that KLF4 modulates wt-CFTR (but not F508del-CFTR) via both the serine/threonine kinase AKT1 (AKT) and glycogen synthase kinase 3 beta (GSK3β) signaling. While AKT acts positively, GSK3β is a negative regulator of CFTR. This crosstalk between wt-CFTR and KLF4 via AKT/ GSK3β signaling, which is disrupted in CF, constitutes a novel mechanism linking CFTR to the epithelial differentiation.
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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.