ArticleOncogene2015
The P2X7 receptor is a key modulator of the PI3K/GSK3β/VEGF signaling network: evidence in experimental neuroblastoma.
Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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Who cites it
117 citing papers in PubMed, 198 citations in OpenAlex.
- Identification of the promoter region of the human P2RX7 gene.Purinergic signalling · 2026Article
- Methodological guidelines for P2X receptor assays and data interpretation.Cell death & disease · 2026Review
- Latest advances on the role of P2X Receptors in colorectal inflammation and cancer.Purinergic signalling · 2026Review
- Reconstruction of an extensive gouty tophus ulceration at the wrist using a dermal matrix and autologous skin graft: A case report.JPRAS open · 2026Article
- Single-Cell Transcriptomic Profiling of GL261 Glioblastoma Cells Reveals Gene Expression Signatures Underlying Tumorigenicity.Cellular and molecular neurobiology · 2025Article
- Genetic Variations in the P2X7 Receptor: Opportunities and Challenges for Drug Development.International journal of molecular sciences · 2025Review
- Characterisation of the expression of P2X7 receptor, cancer stem cell markers and immunological mediators in human high-grade gliomas.BMC neuroscience · 2025Article
- Targeting the Purinergic Axis with Phenolic Compounds to Disrupt the Oxidative-Inflammatory Cycle in Thyroid Cancer.International journal of molecular sciences · 2025Review
- P2X7 a new therapeutic target to block vesicle-dependent metastasis in colon carcinoma: Role of the A2A/CD39/CD73 axis.Cell death & disease · 2025Article
- Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.Purinergic signalling · 2025Review
- Antagonism of the ATP-gated P2X7 receptor inhibits the proliferation of hepatocellular carcinoma cells.Purinergic signalling · 2025Article
- New insights into pathogenisis and therapies of P2X7R in Parkinson's disease.NPJ Parkinson's disease · 2025Review
- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
- Transcriptome Analysis Suggests PKD3 Regulates Proliferative Glucose Metabolism, Calcium Homeostasis and Microtubule Dynamics After MEF Spontaneous Immortalization.International journal of molecular sciences · 2025Article
- Targeting Retinal Neuroglial Vascular Unit Damage: Novel Therapeutic Strategies for Early-Stage Diabetic Retinopathy.Journal of diabetes research · 2025Review
- Leveraging adenosine triphosphate for cancer theranostics.Theranostics · 2025Review
- Article
- Role of P2X7 receptor in the progression and clinicopathological characteristics of gastric cancer.Scientific reports · 2024Article
- Comparison of the efficiency of ultrafiltration, precipitation, and ultracentrifugation methods for exosome isolation.Biochemistry and biophysics reports · 2024Article
- Antifibrotic effect of the P2X7 receptor antagonist A740003 against acute myocardial infarction-induced fibrotic remodelling.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2024Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroblastoma (NB) is an aggressive pediatric tumor, responsible for 15% of cancer-related deaths in childhood, lacking an effective treatment in its advanced stages. The P2X7 receptor for extracellular ATP was associated to NB cell proliferation and recently emerged as a promoter of tumor engraftment, growth and vascularization. In an effort to identify new therapeutic options for neuroblastoma, we studied the role of P2X7 receptor in NB biology. We first analyzed the effect of P2X7 activation or down-modulation of the main biochemical ways involved in NB progression: the PI3K/Akt/GSK3β/MYCN and the HIF1α/VEGF pathways. In ACN human NB cells, P2X7 stimulation enhanced PI3K/Akt, while decreasing GSK3β activity. In the same model, P2X7 silencing or antagonist administration reduced the activity of PI3K/Akt and increased that of GSK3β, leading to a decrease in cellular glycogen stores. Similarly, P2X7 downmodulation caused a reduction in HIF1α levels and vascular endothelial growth factor (VEGF) secretion. Systemic administration of two different P2X7 antagonists (AZ10606120 or A740003) in nude/nude mice reduced ACN-derived tumor growth. An even stronger effect of P2X7 blockade was obtained in a syngeneic immune-competent neuroblastoma model: Neuro2A cells injected in AlbinoJ mice. Together with tumor regression, treatment with P2X7 antagonists caused downmodulation of the Akt/HIF1α axis, leading to reduced VEGF content and decreased vessel formation. Interestingly, in both experimental models, P2X7 antagonists strongly reduced the expression of the probably best-accepted oncogene in NB: MYCN. Finally, we associated P2X7 overexpression with poor prognosis in advanced-stage NB patients. Taken together, our data suggest that P2X7 receptor is an upstream regulator of the main signaling pathways involved in NB growth, metabolic activity and angiogenesis, and a promising therapeutic target for neuroblastoma treatment.
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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.