ArticleThe Journal of clinical investigation2012
P14ARF inhibits human glioblastoma-induced angiogenesis by upregulating the expression of TIMP3.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 71 citations in OpenAlex.
- Homozygous CDKN2A/B deletions in low- and high-grade glioma: a meta-analysis of individual patient data and predictive values of p16 immunohistochemistry testing.Acta neuropathologica communications · 2024Pooled it
- CDKN2A/B deletions are strongly associated with meningioma progression: a meta-analysis of individual patient data.Acta neuropathologica communications · 2023Pooled it
- Identification of hsa-miR-144-3p as a novel immunotherapeutic target for glioblastoma based on disulfidptosis-related analysis.Discover oncology · 2026Article
- circSH3GL3 inhibits glioma progression and invasion via regulating the PI3K/AKT and Wnt/β-catenin signaling pathways by competitively binding with miR-21-5p.Molecular and cellular biochemistry · 2026Article
- Unraveling the role of specificity protein 1 in gliomas: pathophysiology and clinical implications.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Bridging cancer cell-intrinsic driver genes and -extrinsic cell-cell communication with Driver2Comm.PLoS computational biology · 2026Article
- Integrating Multiplex Immunohistochemistry and Machine Learning for Glioma Subtyping and Prognosis Prediction.MedComm · 2025Article
- Novel CHI3L1-Associated Angiogenic Phenotypes Define Glioma Microenvironments: Insights From Multi-Omics Integration.Cancer science · 2025Article
- The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma.Epigenomics · 2025Review
- The two-sided battlefield of tumour-associated macrophages in glioblastoma: unravelling their therapeutic potential.Discover oncology · 2024Review
- Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review.Cancers · 2023Review
- Review
- Qualitative and Quantitative Magnetic Resonance Imaging Phenotypes May Predict CDKN2A/B Homozygous Deletion Status in Isocitrate Dehydrogenase-Mutant Astrocytomas: A Multicenter Study.Korean journal of radiology · 2023Article
- Translational significance of CDKN2A/B homozygous deletion in isocitrate dehydrogenase-mutant astrocytoma.Neuro-oncology · 2023Review
- Aptamers for Addressed Boron Delivery in BNCT: Effect of Boron Cluster Attachment Site on Functional Activity.International journal of molecular sciences · 2022Article
- The novel histone deacetylase inhibitor pracinostat suppresses the malignant phenotype in human glioma.Molecular biology reports · 2022Article
- Interrogating glioma-M2 macrophage interactions identifies Gal-9/Tim-3 as a viable target againstScience advances · 2022Article
- Context-Dependent Glioblastoma-Macrophage/Microglia Symbiosis and Associated Mechanisms.Trends in immunology · 2021Review
- P-selectin axis plays a key role in microglia immunophenotype and glioblastoma progression.Nature communications · 2021Article
- TARBP2 promotes tumor angiogenesis and metastasis by destabilizing antiangiogenic factor mRNAs.Cancer science · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Malignant gliomas are the most common and the most lethal primary brain tumors in adults. Among malignant gliomas, 60%-80% show loss of P14ARF tumor suppressor activity due to somatic alterations of the INK4A/ARF genetic locus. The tumor suppressor activity of P14ARF is in part a result of its ability to prevent the degradation of P53 by binding to and sequestering HDM2. However, the subsequent finding of P14ARF loss in conjunction with TP53 gene loss in some tumors suggests the protein may have other P53-independent tumor suppressor functions. Here, we report what we believe to be a novel tumor suppressor function for P14ARF as an inhibitor of tumor-induced angiogenesis. We found that P14ARF mediates antiangiogenic effects by upregulating expression of tissue inhibitor of metalloproteinase-3 (TIMP3) in a P53-independent fashion. Mechanistically, this regulation occurred at the gene transcription level and was controlled by HDM2-SP1 interplay, where P14ARF relieved a dominant negative interaction of HDM2 with SP1. P14ARF-induced expression of TIMP3 inhibited endothelial cell migration and vessel formation in response to angiogenic stimuli produced by cancer cells. The discovery of this angiogenesis regulatory pathway may provide new insights into P53-independent P14ARF tumor-suppressive mechanisms that have implications for the development of novel therapies directed at tumors and other diseases characterized by vascular pathology.
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.