ArticleCancer research2012
Fibulin-3 promotes glioma growth and resistance through a novel paracrine regulation of Notch signaling.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07243470 (A Multicenter, Open-label Phase I/II Trial Aiming to Assess the Safety and Clinical Activity of Tarlatamab in Combination With Metronomic Temozolomide in Adolescents and Adults' Patients With High Grade Brain Tumors), which is not on this map. Cited by 56 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.
A Multicenter, Open-label Phase I/II Trial Aiming to Assess the Safety and Clinical Activity of Tarlatamab in Combination With Metronomic Temozolomide in Adolescents and Adults' Patients With High Grade Brain Tumors
Who cites it
56 citing papers in PubMed, 91 citations in OpenAlex.
- Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.Circulation. Cardiovascular genetics · 2015Trial
- Inhibition of Extracellular Matrix Protein Fibulin-3 Reduces Immunosuppressive Signaling and Increases Macrophage Activation in Glioblastoma.Cancer research communications · 2025Article
- Targeting DLL3: Innovative Strategies for Tumor Treatment.Pharmaceutics · 2025Review
- Biosensor-Enhanced Organ-on-a-Chip Models for Investigating Glioblastoma Tumor Microenvironment Dynamics.Sensors (Basel, Switzerland) · 2024Review
- Mechanism of Notch Signaling Pathway in Malignant Progression of Glioblastoma and Targeted Therapy.Biomolecules · 2024Review
- Engineering the glioblastoma microenvironment with bioactive nanoparticles for effective immunotherapy.RSC advances · 2023Review
- Fibulin2: a negative regulator of BMSC osteogenic differentiation in infected bone fracture healing.Experimental & molecular medicine · 2023Article
- EFEMP1 binds to STEAP1 to promote osteosarcoma proliferation and invasion via the Wnt/β-catenin and TGF-β/Smad2/3 signal pathways.Journal of bone oncology · 2022Article
- Significance of fibulin-3 expression in bladder cancer: a tissue microarray-based immunohistochemical study.World journal of surgical oncology · 2022Article
- Comprehensive omics analyses profile genesets related with tumor heterogeneity of multifocal glioblastomas and reveal LIF/CCL2 as biomarkers for mesenchymal subtype.Theranostics · 2022Article
- The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling.Frontiers in oncology · 2022Article
- METTL1-mClinical and translational medicine · 2021Article
- Integrated Gene Expression and Methylation Analyses Identify DLL3 as a Biomarker for Prognosis of Malignant Glioma.Journal of molecular neuroscience : MN · 2021Article
- Article
- Extracellular matrix in glioblastoma: opportunities for emerging therapeutic approaches.American journal of cancer research · 2021Review
- Molecular Mechanisms of Treatment Resistance in Glioblastoma.International journal of molecular sciences · 2020Review
- The Pathophysiological Significance of Fibulin-3.Biomolecules · 2020Review
- miR-338-5p Targets Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 to Inhibit the Growth and Invasion of Trophoblast Cells in Selective Intrauterine Growth Restriction.Reproductive sciences (Thousand Oaks, Calif.) · 2020Article
- Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment.Frontiers in cellular neuroscience · 2020Review
- Increased Expression of Fibulin-1 Is Associated With Hepatocellular Carcinoma Progression by Regulating the Notch Signaling Pathway.Frontiers in cell and developmental biology · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Malignant gliomas are highly invasive and chemoresistant brain tumors with extremely poor prognosis. Targeting of the soluble factors that trigger invasion and resistance, therefore, could have a significant impact against the infiltrative glioma cells that are a major source of recurrence. Fibulin-3 is a matrix protein that is absent in normal brain but upregulated in gliomas and promotes tumor invasion by unknown mechanisms. Here, we show that fibulin-3 is a novel soluble activator of Notch signaling that antagonizes DLL3, an autocrine inhibitor or Notch, and promotes tumor cell survival and invasion in a Notch-dependent manner. Using a strategy for inducible knockdown, we found that controlled downregulation of fibulin-3 reduced Notch signaling and led to increased apoptosis, reduced self-renewal of glioblastoma-initiating cells, and impaired growth and dispersion of intracranial tumors. In addition, fibulin-3 expression correlated with expression levels of Notch-dependent genes and was a marker of Notch activation in patient-derived glioma samples. These findings underscore a major role for the tumor extracellular matrix in regulating glioma invasion and resistance to apoptosis via activation of the key Notch pathway. More importantly, this work describes a noncanonical, soluble activator of Notch in a cancer model and shows how Notch signaling can be reduced by targeting tumor-specific accessible molecules in the tumor microenvironment.
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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.