ArticleNeoplasia (New York, N.Y.)2012
Netrin-4 promotes glioblastoma cell proliferation through integrin β4 signaling.
Article in Neoplasia (New York, N.Y.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
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Who cites it
35 citing papers in PubMed, 46 citations in OpenAlex.
- Comprehensive pan-cancer analysis reveals NTN1 as an immune infiltrate risk factor and its potential prognostic value in SKCM.Scientific reports · 2025Article
- Research progress of the netrins and their receptors in cancer.Journal of cellular and molecular medicine · 2024Review
- EXOSC5 maintains cancer stem cell activity in endometrial cancer by regulating the NTN4/integrin β1 signalling axis.International journal of biological sciences · 2024Article
- Netrin-4: Focus on Its Role in Axon Guidance, Tissue Stability, Angiogenesis and Tumors.Cellular and molecular neurobiology · 2023Review
- Article
- Regulation of Kinase Signaling Pathways by α6β4-Integrins and Plectin in Prostate Cancer.Cancers · 2022Review
- Fate mapping of neural stem cell niches reveals distinct origins of human cortical astrocytes.Science (New York, N.Y.) · 2022Article
- The risk variant rs11836367 contributes to breast cancer onset and metastasis by attenuating Wnt signaling via regulatingScience advances · 2022Article
- Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker.Biomolecules · 2021Review
- Transcriptomics-Based Phenotypic Screening Supports Drug Discovery in Human Glioblastoma Cells.Cancers · 2021Article
- Basement membrane stiffness determines metastases formation.Nature materials · 2021Article
- Rapid 3D Bioprinting of Glioblastoma Model Mimicking Native Biophysical Heterogeneity.Small (Weinheim an der Bergstrasse, Germany) · 2021Article
- Elevated RGMA Expression Predicts Poor Prognosis in Patients with Glioblastoma.OncoTargets and therapy · 2021Article
- Expression Profiling of Glioblastoma Cell Lines Reveals Novel Extracellular Matrix-Receptor Genes Correlated With the Responsiveness of Glioma Patients to Ionizing Radiation.Frontiers in oncology · 2021Article
- The pan-cancer landscape of netrin family reveals potential oncogenic biomarkers.Scientific reports · 2020Article
- Involvement of Netrins and Their Receptors in Neuronal Migration in the Cerebral Cortex.Frontiers in cell and developmental biology · 2020Review
- Netrin Family: Role for Protein Isoforms in Cancer.Journal of nucleic acids · 2019Review
- EGF/EGFR upregulates and cooperates with Netrin-4 to protect glioblastoma cells from DNA damage-induced senescence.BMC cancer · 2018Article
- SEC-induced activation of ANXA7 GTPase suppresses prostate cancer metastasis.Cancer letters · 2018Article
- Molecular characterization of pro-metastatic functions of β4-integrin in colorectal cancer.Oncotarget · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Netrin-4 is a laminin-related secreted molecule originally found to have roles in neuronal axon migration. Recent studies have indicated that netrin-4 also participates in the development of nonneural tissues and modulates tumor cell proliferation and tumor metastasis. Here we have explored the functions and molecular mechanisms of netrin-4 in glioblastoma multiforme. The suppression of netrin-4 expression in glioblastoma cell lines significantly reduced cell proliferation and motility and increased serum deprivation-induced apoptosis. Using tandem affinity purification combined with protein identification by mass spectrometry, we found that integrin β(4) interacts with netrin-4 and that it mediates mitogenic effects as well as AKT and mammalian target of rapamycin phosphorylation induced by netrin-4. Interestingly, netrin-4 acted as an inhibitor of cell proliferation in integrin β(4)-silenced glioblastoma cells, and high concentrations of netrin-4 reduced cell proliferation. The negative effects of netrin-4 on proliferation were mediated by UNC5B. Analysis of more than 400 primary tumors from The Cancer Genome Atlas repository revealed that the expression of netrin-4 is significantly downregulated in glioblastoma and that the reduced expression is linked to poor patient survival time. The expression of integrin β(4) is increased in glioblastoma, and it predicts poor patient survival time. Current results illustrate a novel mechanism for glioma progression, where glioma cells reduce netrin-4 expression to decrease its inhibitory effects. In parallel, the expression of integrin β(4) is upregulated to sensitize the cells to low concentrations of netrin-4 for maintaining cell proliferation.
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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.