ArticleProceedings of the National Academy of Sciences of the United States of America2010
Inositol-requiring enzyme 1alpha is a key regulator of angiogenesis and invasion in malignant glioma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
135 citing papers in PubMed, 2 syntheses or guidelines pooled it, 347 citations in OpenAlex.
- ER stress as a trigger of UPR and ER-phagy in cancer growth and spread.Frontiers in oncology · 2022Pooled it
- Systematic review of protein biomarkers of invasive behavior in glioblastoma.Molecular neurobiology · 2014Pooled it
- Differential gene expression in glioblastoma defined by ADC histogram analysis: relationship to extracellular matrix molecules and survival.AJNR. American journal of neuroradiology · 2012Trial
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Deciphering the interplay between hypoxia, angiogenesis, and endoplasmic reticulum stress in carcinogenesis: A narrative review.World journal of experimental medicine · 2026Review
- Machine-learning assisted subclassification of glioblastoma by developing an endoplasmic reticulum stress-related methylation signature.Frontiers in oncology · 2026Article
- Review
- Leukocyte-intrinsic ER stress responses contribute to chemotherapy-induced peripheral neuropathy.Science translational medicine · 2025Article
- Somatic mutations in IRE1α regulate keratinocyte migration and survival by differentially activating Rho GTPases.Journal of cell science · 2025Article
- Endoplasmic Reticulum Stress in Cancer.MedComm · 2025Review
- Impact of ATF6 deletion on the embryonic brain development.iScience · 2025Article
- Review
- Endoplasmic Reticulum Stress: Implications in Diseases.The protein journal · 2025Review
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Inhibition of PERK-mediated unfolded protein response acts as a switch for reversal of residual senescence and as senolytic therapy in glioblastoma.Neuro-oncology · 2024Article
- Endoplasmic reticulum stress-a key guardian in cancer.Cell death discovery · 2024Review
- The unfolded protein response machinery in glioblastoma genesis, chemoresistance and as a druggable target.CNS neuroscience & therapeutics · 2024Review
- ZO-1 interacts with YB-1 in endothelial cells to regulate stress granule formation during angiogenesis.Nature communications · 2024Article
- IRE1 endoribonuclease signaling promotes myeloid cell infiltration in glioblastoma.Neuro-oncology · 2024Article
- Impact of Obesity-Related Endoplasmic Reticulum Stress on Cancer and Associated Molecular Targets.Biomedicines · 2024Review
75 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inositol-requiring enzyme 1 (IRE1) is a proximal endoplasmic reticulum (ER) stress sensor and a central mediator of the unfolded protein response. In a human glioma model, inhibition of IRE1alpha correlated with down-regulation of prevalent proangiogenic factors such as VEGF-A, IL-1beta, IL-6, and IL-8. Significant up-regulation of antiangiogenic gene transcripts was also apparent. These transcripts encode SPARC, decorin, thrombospondin-1, and other matrix proteins functionally linked to mesenchymal differentiation and glioma invasiveness. In vivo, using both the chick chorio-allantoic membrane assay and a mouse orthotopic brain model, we observed in tumors underexpressing IRE1: (i) reduction of angiogenesis and blood perfusion, (ii) a decreased growth rate, and (iii) extensive invasiveness and blood vessel cooption. This phenotypic change was consistently associated with increased overall survival in glioma-implanted recipient mice. Ectopic expression of IL-6 in IRE1-deficient tumors restored angiogenesis and neutralized vessel cooption but did not reverse the mesenchymal/infiltrative cell phenotype. The ischemia-responsive IRE1 protein is thus identified as a key regulator of tumor neovascularization and invasiveness.
Indexed as
Identifiers
What OpenQuestion holds
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.