ArticleCancer research2009
Epidermal growth factor receptor and PTEN modulate tissue factor expression in glioblastoma through JunD/activator protein-1 transcriptional activity.
Article in Cancer research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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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
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 129 citations in OpenAlex.
- Tissue factor in tumor microenvironment: a systematic review.Journal of hematology & oncology · 2014Pooled it
- Matrix stress relaxation promotes glioblastoma cell migration in a ligand-specific manner.Scientific reports · 2026Article
- Venous Thromboembolism in Patients with Glioblastoma: Molecular Mechanisms and Clinical Implications.Thrombosis and haemostasis · 2025Review
- A clinically relevant model and method to study necrosis as a driving force in glioma restructuring and progression.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Selective but not pan-CDK inhibition abrogates 5-FU-driven tissue factor upregulation in colon cancer.Scientific reports · 2024Article
- The Role of Tissue Factor In Signaling Pathways of Pathological Conditions and Angiogenesis.Current molecular medicine · 2024Review
- EML4-ALK fusion protein in Lung cancer cells enhances venous thrombogenicity through the pERK1/2-AP-1-tissue factor axis.Journal of thrombosis and thrombolysis · 2024Article
- TF/PAR2 Signaling Axis Supports the Protumor Effect of Neutrophil Extracellular Traps (NETs) on Human Breast Cancer Cells.Cancers · 2023Article
- The Role of EGFR Amplification in Deep Venous Thrombosis Occurrence in IDH Wild-Type Glioblastoma.Current oncology (Toronto, Ont.) · 2023Article
- The Tissue Factor Pathway in Cancer: Overview and Role of Heparan Sulfate Proteoglycans.Cancers · 2023Review
- Regulation of Tissue Factor by CD44 Supports Coagulant Activity in Breast Tumor Cells.Cancers · 2022Article
- Combined analysis of clinical and laboratory markers to predict the risk of venous thromboembolism in patients with IDH1 wild-type glioblastoma.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Article
- Factor VIII as a potential player in cancer pathophysiology.Journal of thrombosis and haemostasis : JTH · 2022Article
- Cancer-associated venous thromboembolism.Nature reviews. Disease primers · 2022Review
- The probable role and therapeutic potential of the PI3K/AKT signaling pathway in SARS-CoV-2 induced coagulopathy.Cellular & molecular biology letters · 2022Review
- Biological implications and clinical potential of invasion and migration related miRNAs in glioma.Frontiers in integrative neuroscience · 2022Review
- A Novel Thrombosis-Related Signature for Predicting Survival and Drug Compounds in Glioblastoma.Journal of oncology · 2022Article
- Tumor Cell-Induced Platelet Aggregation as an Emerging Therapeutic Target for Cancer Therapy.Frontiers in oncology · 2022Review
- Interleukin-1β Induces Tissue Factor Expression in A549 Cells via EGFR-Dependent and -Independent Mechanisms.International journal of molecular sciences · 2021Article
- Risk of Venous Thromboembolism in Grade II-IV Gliomas as a Function of Molecular Subtype.Neurology · 2021Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Hypoxia and necrosis are fundamental features of glioblastoma (GBM) and their emergence is critical for the rapid biological progression of this fatal tumor; yet, underlying mechanisms are poorly understood. We have suggested that vaso-occlusion following intravascular thrombosis could initiate or propagate hypoxia and necrosis in GBM. Tissue factor (TF), the main cellular initiator of coagulation, is overexpressed in GBMs and likely favors a thrombotic microenvironment. Epidermal growth factor receptor (EGFR) amplification and PTEN loss are two common genetic alterations seen in GBM but not in lower-grade astrocytomas that could be responsible for TF up-regulation. The most frequent EGFR mutation in GBM involves deletion of exons 2 to 7, resulting in the expression of a constitutively active receptor, EGFRvIII. Here, we show that overexpression of EGFR or EGFRvIII in human glioma cells causes increased basal TF expression and that stimulation of EGFR by its ligand, EGF, leads to a marked dose-dependent up-regulation of TF. In all cases, increased TF expression led to accelerated plasma coagulation in vitro. EGFR-mediated TF expression depended most strongly on activator protein-1 (AP-1) transcriptional activity and was associated with c-Jun NH(2)-terminal kinase (JNK) and JunD activation. Restoration of PTEN expression in PTEN-deficient GBM cells diminished EGFR-induced TF expression by inhibiting JunD/AP-1 transcriptional activity. PTEN mediated this effect by antagonizing phosphatidylinositol 3-kinase activity, which in turn attenuated both Akt and JNK activities. These mechanisms are likely at work in vivo, as EGFR expression was highly correlated with TF expression in human high-grade astrocytoma specimens.
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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.