ArticleMolecular cancer2015
The P2X7 receptor regulates cell survival, migration and invasion of pancreatic ductal adenocarcinoma cells.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 125 citations in OpenAlex.
- Iron and Other Metal Ions in Human Health and Disease.MedComm · 2026Review
- ARHI as a key regulator of EMT and metastasis in pancreatic cancer via the Notch-1 pathway.Human genetics · 2026Article
- TGM2-P2RX7 loop promotes gemcitabine resistance in pancreatic cancer by modulating glutamine metabolism and mitophagy.Cell death discovery · 2025Article
- P2RX7 modulates the function of human microglia-like cells and mediates the association of IL18 with Alzheimer's disease traits.Neurobiology of disease · 2025Article
- Functional role of P2X7 purinergic receptor in cancer and cancer-related pain.Purinergic signalling · 2025Review
- The functional role of P2 purinergic receptors in the progression of gastric cancer.Purinergic signalling · 2025Review
- Antagonism of the ATP-gated P2X7 receptor inhibits the proliferation of hepatocellular carcinoma cells.Purinergic signalling · 2025Article
- P2X7 receptor promotes the growth and metastasis of gastric cancer by activating P13/AKT/GSK-3 beta signaling (experimental research).International journal of surgery (London, England) · 2025Article
- Dys-regulated phosphatidylserine externalization as a cell intrinsic immune escape mechanism in cancer.Cell communication and signaling : CCS · 2025Review
- Purinergic system in cancer stem cells.Purinergic signalling · 2025Review
- The Role of the Dysregulation of circRNAs Expression in Glioblastoma Multiforme.Journal of molecular neuroscience : MN · 2025Review
- Conventional Chemotherapy and Inflammation: What Is the Role of the Inflammasome in the Tumor Microenvironment?Biomedicines · 2025Review
- Article
- P2X7 Variants in Pathophysiology.International journal of molecular sciences · 2024Review
- Human P2X7 receptor variants Gly150Arg and Arg276His polymorphisms have differential effects on risk association and cellular functions in pancreatic cancer.Cancer cell international · 2024Article
- Implications of NLRP3 Suppression Using Glibenclamide and miR-223 against Colorectal Cancer.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Extracellular ATP/P2X7 receptor, a regulatory axis of migration in ovarian carcinoma-derived cells.PloS one · 2024Article
- P2X7 receptor promotes migration and invasion of non-small cell lung cancer A549 cells through the PI3K/Akt pathways.Purinergic signalling · 2023Article
- Purine and purinergic receptors in health and disease.MedComm · 2023Review
- Tetracyclic 1,4-Naphthoquinone Thioglucoside Conjugate U-556 Blocks the Purinergic P2X7 Receptor in Macrophages and Exhibits Anti-Inflammatory Activity In Vivo.International journal of molecular sciences · 2023Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is presently one of the cancers with the worst survival rates and least effective treatments. Moreover, total deaths due to PDAC are predicted to increase in the next 15 years. Therefore, novel insights into basic mechanism of PDAC development and therapies are needed. PDAC is characterized by a complex microenvironment, in which cancer and stromal cells release different molecules, such as ATP. ATP can be transported and/or exocytosed from active cancer cells and released from dying cells in the necrotic core of the cancer. We hypothesized that one of the ATP receptors, the P2X7 receptor (P2X7R) could be an important player in PDAC behaviour.
methodsWe determined the expression (real time PCR and Western blot) and localization (immunofluorescence) of P2X7R in human PDAC cell lines (AsPC-1, BxPC-3, Capan-1, MiaPaCa-2, Panc-1) and a "normal" human pancreatic duct epithelial cell line (HPDE). The function of P2X7R in proliferation (BrdU assay), migration (wound assay) and invasion (Boyden chamber with matrigel) was characterized. Furthermore, we studied P2X7R-dependent pore formation (YoPro-1 assay) and cell death (caspase and annexin V / propidium iodide assays).
resultsWe found higher expression of P2X7R protein in PDAC compared to HPDE cells. P2X7R had notable disparate effects on PDAC survival. Firstly, high concentrations of ATP or the specific P2X7R agonist, BzATP, had cytotoxic effects in all cell lines, and cell death was mediated by necrosis. Moreover, the P2X7R-pore antagonist, A438079, prevented ATP-induced pore formation and cell death. Second, in basal conditions and with low concentrations of ATP/BzATP, the P2X7R allosteric inhibitor AZ10606120 reduced proliferation in all PDAC cell lines. P2X7R also affected other key characteristics of cancer cell behavior. AZ10606120 reduced cell migration and invasion in PDAC cell lines compared to that of untreated/vehicle-treated control cells, and stimulation with sub-millimolar concentrations of ATP or BzATP substantially increased cell invasion.
conclusionsPDAC cell lines overexpress P2X7R and the receptor plays crucial roles in cell survival, migration and invasion. Therefore, we propose that drugs targeting P2X7R could be exploited in therapy of pancreatic cancer.
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