ArticleScientific reports2015
PI3K/Akt signaling pathway triggers P2X7 receptor expression as a pro-survival factor of neuroblastoma cells under limiting growth conditions.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 71 citations in OpenAlex.
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- Protective Effect of Silymarin Against Paclitaxel-Induced Cardiotoxicity.Food science & nutrition · 2026Article
- NLRX1 Drives Prostate Cancer Progression Through Activation of AKT and ERK Signaling Pathways.International journal of biological sciences · 2026Article
- Emerging Role of Tripartite Synaptic Transmission in the Pathomechanism of Autosomal-Dominant Sleep-Related Hypermotor Epilepsy.International journal of molecular sciences · 2025Review
- Hepatitis B virus-infected hepatocytes promote the secretion of collagen VI to the extracellular matrix.Scientific reports · 2025Article
- Role and Therapeutic Potential of P2X7 Receptor in Lung Cancer Progression.Current medicinal chemistry · 2025Review
- DUSP1/MKP-1 represents another piece in the P2X7R intracellular signaling puzzle in cerebellar cells: our last journey with Mª Teresa along the purinergic pathways of Eden.Purinergic signalling · 2024Article
- Article
- Age-Dependent Activation of Purinergic Transmission Contributes to the Development of Epileptogenesis in ADSHE Model Rats.Biomolecules · 2024Article
- P2X7 receptor promotes migration and invasion of non-small cell lung cancer A549 cells through the PI3K/Akt pathways.Purinergic signalling · 2023Article
- The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications.Cancers · 2022Review
- BCI, an inhibitor of the DUSP1 and DUSP6 dual specificity phosphatases, enhances P2X7 receptor expression in neuroblastoma cells.Frontiers in cell and developmental biology · 2022Article
- Ligand-Gated Ion Channels as Targets for Treatment and Management of Cancers.Frontiers in physiology · 2022Review
- 5,8-Dihydroxy-4 ', 7-dimethoxyflavone Attenuates TNF-Oxidative medicine and cellular longevity · 2022Article
- Antagonism of the ATP-gated P2X7 receptor: a potential therapeutic strategy for cancer.Purinergic signalling · 2021Review
- Salient brain entities labelled in P2rx7-EGFP reporter mouse embryos include the septum, roof plate glial specializations and circumventricular ependymal organs.Brain structure & function · 2021Article
- P2X7 Receptors: An Untapped Target for the Management of Cardiovascular Disease.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- To Inhibit or Enhance? Is There a Benefit to Positive Allosteric Modulation of P2X Receptors?Frontiers in pharmacology · 2020Review
- Thy-1 (CD90)-Induced Metastatic Cancer Cell Migration and Invasion Are β3 Integrin-Dependent and Involve a CaFrontiers in cell and developmental biology · 2020Article
- P2X7 in Cancer: From Molecular Mechanisms to Therapeutics.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of purinergic P2X7 receptor (P2X7R) in neuroblastoma cells is associated to accelerated growth rate, angiogenesis, metastasis and poor prognosis. Noticeably, P2X7R allows the survival of neuroblastoma cells under restrictive conditions, including serum and glucose deprivation. Previously we identified specificity protein 1 (Sp1) as the main factor involved in the transcriptional regulation of P2rx7 gene, reporting that serum withdrawal triggers the expression of P2X7R in Neuro-2a (N2a) neuroblastoma cell line. Here we demonstrate that PI3K/Akt pathway is crucial for the upregulation of P2X7R expression in serum-deprived neuroblastoma cells, circumstance that facilitates cell proliferation in the absence of trophic support. The effect exerted by PI3K/Akt is independent of both mTOR and GSK3, but requires the activation of EGF receptor (EGFR). Nuclear levels of Sp1 are strongly reduced by inhibition of PI3K/Akt pathway, and blockade of Sp1-dependent transcription with mithramycin A prevents upregulation of P2rx7 gene expression following serum withdrawal. Furthermore, atypical PKCζ plays a key role in the regulation of P2X7R expression by preventing phosphorylation and, consequently, activation of Akt. Altogether, these data indicate that activation of EGFR enhanced the expression of P2X7R in neuroblastoma cells lacking trophic support, being PI3K/Akt/PKCζ signaling pathway and Sp1 mediating this pro-survival outcome.
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