ArticleJournal of experimental & clinical cancer research : CR2019
NKAP alters tumor immune microenvironment and promotes glioma growth via Notch1 signaling.
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. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Molecular Pathogenesis of Glioblastoma in Adults and Future Perspectives: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Unconventional guardians of the brain: MAIT cells as emerging players in glioblastoma immunity.Frontiers in immunology · 2026Review
- NKAP overexpression promotes gastric cancer immune escape by inducing IL-10 secretion from mature dendritic cells during anti-PD-L1 therapy.Journal of gastrointestinal oncology · 2025Article
- Notch signaling pathway in cancer: from mechanistic insights to targeted therapies.Signal transduction and targeted therapy · 2024Review
- DNA Damage-Induced Apoptosis Suppressor Triggers Progression and Stemness of Glioma by Enhancing Lymphoid Enhancer-Binding Factor 1 Expression.World journal of oncology · 2024Article
- Article
- Targeting Options of Tumor-Associated Macrophages (TAM) Activity in Gliomas.Current neuropharmacology · 2023Review
- miR-30c plays diagnostic and prognostic roles and mediates epithelial-mesenchymal transition (EMT) and proliferation of gliomas by affecting Notch1.Scientific reports · 2022Article
- IL-1β promotes hypoxic vascular endothelial cell proliferation through the miR-24-3p/NKAP/NF-κB axis.Bioscience reports · 2022Article
- RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an mCell death & disease · 2022Article
- Identification and Validation of N6-Methyladenosine-Related Biomarkers for Bladder Cancer: Implications for Immunotherapy.Frontiers in oncology · 2022Article
- Discovery of Notch Pathway-Related Genes for Predicting Prognosis and Tumor Microenvironment Status in Bladder Cancer.Frontiers in genetics · 2022Article
- High-throughput microfluidic 3D biomimetic model enabling quantitative description of the human breast tumor microenvironment.Acta biomaterialia · 2021Article
- A novel lncRNA ARST represses glioma progression by inhibiting ALDOA-mediated actin cytoskeleton integrity.Journal of experimental & clinical cancer research : CR · 2021Article
- lncRNA-Xist/miR-101-3p/KLF6/C/EBPα axis promotes TAM polarization to regulate cancer cell proliferation and migration.Molecular therapy. Nucleic acids · 2021Article
- CREBBP/EP300 mutations promoted tumor progression in diffuse large B-cell lymphoma through altering tumor-associated macrophage polarization via FBXW7-NOTCH-CCL2/CSF1 axis.Signal transduction and targeted therapy · 2021Article
- SNAP25 Inhibits Glioma Progression by Regulating Synapse PlasticityFrontiers in oncology · 2021Article
- A computational guided, functional validation of a novel therapeutic antibody proposes Notch signaling as a clinical relevant and druggable target in glioma.Scientific reports · 2020Article
- Nuclear Factor-κB Activating Protein Plays an Oncogenic Role in Neuroblastoma Tumorigenesis and Recurrence Through the Phosphatidylinositol 3-Kinase/Protein Kinase B Signaling Pathway.Frontiers in cell and developmental biology · 2020Article
- Molecular and Clinical Characterization of a Novel Prognostic and Immunologic Biomarker FAM111A in Diffuse Lower-Grade Glioma.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGlioma is one of the most aggressive malignant brain tumors which is characterized with highly infiltrative growth and poor prognosis. NKAP (NF-κB activating protein) is a widely expressed 415-amino acid nuclear protein that is overexpressed by gliomas, but its function in glioma was still unknown.
methodsCCK8 and EDU assay was used to examine the cell viability in vitro, and the xenograft models in nude mice were established to explore the roles of NAKP in vivo. The expressions of NKAP, Notch1 and SDF-1 were analyzed by immunofluorescence analysis. The expression of NKAP and Notch1 in glioma and normal human brain samples were analyzed by immunohistochemical analysis. In addition, CHIP, Gene chip, western blot, flow cytometry, immunofluorescence, ELISA and luciferase assay were used to investigate the internal connection between NKAP and Notch1.
resultsHere we showed that overexpression of NKAP in gliomas could promote tumor growth by contributing to a Notch1-dependent immune-suppressive tumor microenvironment. Downregulation of NKAP in gliomas had abrogated tumor growth and invasion in vitro and in vivo. Interestingly, compared to the control group, inhibiting NKAP set up obstacles to tumor-associated macrophage (TAM) polarization and recruitment by decreasing the secretion of SDF-1 and M-CSF. To identify the potential mechanisms involved, we performed RNA sequencing analysis and found that Notch1 appeared to positively correlate with the expression of NKAP. Furthermore, we proved that NKAP performed its function via directly binding to Notch1 promoter and trans-activating it. Notch1 inhibition could alleviate NKAP's gliomagenesis effects.
conclusionthese observations suggest that NKAP promotes glioma growth by TAM chemoattraction through upregulation of Notch1 and this finding introduces the potential utility of NKAP inhibitors for glioma therapy.
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Registered trials
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