ArticleCancer research2012
Endothelial expression of TNF receptor-1 generates a proapoptotic signal inhibited by integrin α6β1 in glioblastoma.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 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.
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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
28 citing papers in PubMed, 33 citations in OpenAlex.
- Endothelial cell heterogeneity drives angiogenesis in endometriosis: mechanisms and emerging organoid-based models.Apoptosis : an international journal on programmed cell death · 2026Review
- ABTC-0904: targeting glioma stem cells in GBM: a phase 0/II study of hedgehog pathway inhibitor GDC-0449.Journal of neuro-oncology · 2023Article
- Physiological and Pathological Remodeling of Cerebral Microvessels.International journal of molecular sciences · 2022Review
- Integrin α3β1 promotes vessel formation of glioblastoma-associated endothelial cells through calcium-mediated macropinocytosis and lysosomal exocytosis.Nature communications · 2022Article
- Integrin α6-Targeted Molecular Imaging of Central Nervous System Leukemia in Mice.Frontiers in bioengineering and biotechnology · 2022Article
- Integrin-Mediated Tumorigenesis and Its Therapeutic Applications.Frontiers in oncology · 2022Review
- NADNAR cancer · 2021Article
- TNFα and Immune Checkpoint Inhibition: Friend or Foe for Lung Cancer?International journal of molecular sciences · 2021Review
- Natural Small Molecules Targeting NF-κB Signaling in Glioblastoma.Frontiers in pharmacology · 2021Review
- Engineering Three-Dimensional Tumor Models to Study Glioma Cancer Stem Cells and Tumor Microenvironment.Frontiers in cellular neuroscience · 2020Review
- Palmitoylation is required for TNF-R1 signaling.Cell communication and signaling : CCS · 2019Article
- Pericytes in Glioblastomas: Multifaceted Role Within Tumor Microenvironments and Potential for Therapeutic Interventions.Advances in experimental medicine and biology · 2019Article
- Unleashing endogenous TNF-alpha as a cancer immunotherapeutic.Journal of translational medicine · 2018Review
- Macropinocytosis of Bevacizumab by Glioblastoma Cells in the Perivascular Niche Affects their Survival.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Correlation of higher levels of soluble TNF-R1 with a shorter survival, independent of age, in recurrent glioblastoma.Journal of neuro-oncology · 2017Article
- Contribution of the Microenvironmental Niche to Glioblastoma Heterogeneity.BioMed research international · 2017Review
- Contextual signaling in cancer.Seminars in cell & developmental biology · 2016Review
- C5a induces caspase-dependent apoptosis in brain vascular endothelial cells in experimental lupus.Immunology · 2016Article
- Direct contact with perivascular tumor cells enhances integrin αvβ3 signaling and migration of endothelial cells.Oncotarget · 2016Article
- Glioblastoma Stem Cells Microenvironment: The Paracrine Roles of the Niche in Drug and Radioresistance.Stem cells international · 2016Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Activation of TNF receptor 1 (TNF-R1) can generate signals that promote either apoptosis or survival. In this study, we show that these signals can be determined by the character of the extracellular matrix in the tumor microenvironment. Specifically, through studies of glioblastoma, we showed that TNFα stimulation induced apoptosis of primary brain endothelial cells (EC) attached to collagen or fibronectin (which engage integrins α2β1/α3β1 and α5β1, respectively), but did not induce apoptosis of ECs attached to laminin (which engages integrins α6β1 and α3β1). TNF-R1 expression was significantly higher in ECs in glioblastoma (GBM) tumors compared with ECs in normal brain specimens. TNFα was also expressed in GBM tumor-associated ECs, which was associated with longer patient survival. ECs plated on anti-integrin α2 or α3 antibody were susceptible to TNFα-induced apoptosis, whereas those plated on anti-integrin α6 antibody were not. Moreover, the ECs plated on laminin, but not collagen, expressed cellular FLICE inhibitory protein (cFLIP) and TNFα stimulation of laminin-attached cells in which cFLIP had been downregulated resulted in the induction of apoptosis. In contrast, attachment to laminin did not induce cFLIP expression in GBM tumor stem cells. Together, our findings indicate that the laminin receptor integrin α6β1 promotes the survival of brain ECs by inhibiting prodeath signaling by TNF-R1, in part by inducing cFLIP expression.
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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.