ArticleJournal of experimental & clinical cancer research : CR2019
Reciprocal regulation of integrin β4 and KLF4 promotes gliomagenesis through maintaining cancer stem cell traits.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 36 papers.
What it found
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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
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
36 citing papers in PubMed, 91 citations in OpenAlex.
- A mechanosensitive gene signature associated with immune landscape and survival in glioma: a multi-cohort analysis.Neurological research and practice · 2026Article
- Proteomic Profiling of Endothelial Cells Under Laminar Shear Stress Confirms the Importance of KLF4 in the Regulation of Membrane Protein Expression Compared to Oscillatory Flow.Journal of proteome research · 2026Article
- M2-like GAMs secreting CSTA drive glioblastoma progression via the ITGB4-TGFB1 feedback axis.Journal of translational medicine · 2026Article
- Krüppel-Like Factor 4, a Hub Gate for Cell Crosstalk in Tumor Microenvironment.Cancer medicine · 2026Review
- KLF4 in cancer chemoresistance: molecular mechanisms and therapeutic implications.Discover oncology · 2025Review
- Transcriptomic Profile of Isocitrate Dehydrogenase Mutant Type of Lower-Grade Glioma Reveals Molecular Changes for Prognosis.Biomedicines · 2025Article
- Article
- Integrin signaling in tumor biology: mechanisms of intercellular crosstalk and emerging targeted therapies.PeerJ · 2025Review
- ITGB4 is a prognostic biomarker and correlated with lung adenocarcinoma brain metastasis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Article
- Bufotalin Induces Oxidative Stress-Mediated Apoptosis by Blocking the ITGB4/FAK/ERK Pathway in Glioblastoma.Antioxidants (Basel, Switzerland) · 2024Article
- Machine learning-based identification of biomarkers and drugs in immunologically cold and hot pancreatic adenocarcinomas.Journal of translational medicine · 2024Article
- IDH1-mutant metabolite D-2-hydroxyglutarate inhibits proliferation and sensitizes glioma to temozolomide via down-regulating ITGB4/PI3K/AKT.Cell death discovery · 2024Article
- Deciphering the role of transcription factors in glioblastoma cancer stem cells.Acta biochimica et biophysica Sinica · 2024Review
- KLF transcription factors in bone diseases.Journal of cellular and molecular medicine · 2024Review
- Identification of ITGB4 as a novel tumor promoting gene in lung adenocarcinoma (LUAD).Oncology reports · 2024Article
- ITGB4 upregulation is associated with progression of lower grade glioma.Scientific reports · 2024Article
- The mechanism of ITGB4 in tumor migration and invasion.Frontiers in oncology · 2024Review
- Integrins in cancer stem cells.Frontiers in cell and developmental biology · 2024Review
- Correction: Reciprocal regulation of integrin β4 and KLF4 promotes gliomagenesis through maintaining cancer stem cell traits.Journal of experimental & clinical cancer research : CR · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe dismal prognosis of patients with glioma is largely attributed to cancer stem cells that display pivotal roles in tumour initiation, progression, metastasis, resistance to therapy, and relapse. Therefore, understanding how these populations of cells maintain their stem-like properties is critical in developing effective glioma therapeutics.
methodsRNA sequencing analysis was used to identify genes potentially involved in regulating glioma stem cells (GSCs). Integrin β4 (ITGB4) expression was validated by quantitative real-time PCR (qRT-PCR) and immunohistochemical (IHC) staining. The role of ITGB4 was investigated by flow cytometry, mammosphere formation, transwell, colony formation, and in vivo tumorigenesis assays. The reciprocal regulation between Integrin β4 and KLF4 was investigated by chromatin immunoprecipitation (ChIP), dual-luciferase reporter assay, immunoprecipitation, and in vivo ubiquitylation assays.
resultsIn this study, we found that ITGB4 expression was increased in GSCs and human glioma tissues. Upregulation of ITGB4 was correlated with glioma grades. Inhibition of ITGB4 in glioma cells decreased the self-renewal abilities of GSCs and suppressed the malignant behaviours of glioma cells in vitro and in vivo. Further mechanistic studies revealed that KLF4, an important transcription factor, directly binds to the promoter of ITGB4, facilitating its transcription and contributing to increased ITGB4 expression in glioma. Interestingly, this increased expression enabled ITGB4 to bind KLF4, thus attenuating its interaction with its E3 ligase, the von Hippel-Lindau (VHL) protein, which subsequently decreases KLF4 ubiquitination and leads to its accumulation.
conclusionsCollectively, our data indicate the existence of a positive feedback loop between KLF4 and ITGB4 that promotes GSC self-renewal and gliomagenesis, suggesting that ITGB4 may be a valuable therapeutic target for glioma.
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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 Socratic graph.