{"doi":"10.1093/neuonc/noaf201.0254","title":"CNSC-46. EXTRACELLULAR ATP/ADP PROMOTE GLIOBLASTOMA TUMOR GROWTH THROUGH ACTIVATION OF THE P2Y1 PURINERGIC RECEPTOR AND INDUCTION OF TUMOR CELL-AUTONOMOUS CALCIUM OSCILLATIONS","abstract":"Abstract Glioblastoma (GBM) is the most common and aggressive primary brain malignancy in adults. Recent observations suggest that GBM cells generate cell-autonomous Ca2+ oscillations that promote tumor growth. Here, we investigated extracellular drivers of these oscillations by imaging patient-derived GBM cells (PDGCs) transduced with GCaMP6s, a genetically encoded Ca2+ indicator. Treatment with extracellular ATP and ADP induced robust potentiation of Ca2+ oscillations, suggesting that activation of cell surface purinergic receptors influences the generation of Ca2+ waves. One of the most highly expressed purinergic receptors in GBM, P2Y1, is a Gaq protein-coupled receptor activated by ADP and ATP that promotes Ca2+ release from intracellular stores. We found that both pharmacologic inhibition and shRNA knockdown of P2Y1 in PDGCs reduced spontaneous and ATP/ADP-induced Ca2+ oscillations. Knockdown of P2Y1 also reduced tumor sphere formation and invasion in vitro, indicating an important role for P2Y1 in generating Ca2+ oscillations and driving tumor growth. Furthermore, to determine whether PDGCs actively secrete ATP to contribute to purinergic signaling, we performed an shRNA knockdown of PANX1, a membrane hemichannel that mediates ATP release, and measured extracellular ATP via bioluminescence. The amount of extracellular ATP was reduced from PANX1 knockdown cells compared to a non-targeting control. Together, these experiments demonstrate the importance of purinergic signaling via P2Y1 in generating tumor cell-autonomous Ca2+ waves that drive GBM growth and suggest a role for PANX1 in actively secreting ATP to contribute to this signaling.","journal":"Neuro-Oncology","year":2025,"id":580873,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.957,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1491942,"name":"Shuai Wang","orcid":"0000-0003-3946-4497","position":1,"is_corresponding":false},{"id":1047652,"name":"Sara Haddock","orcid":"0000-0002-5661-5317","position":2,"is_corresponding":false},{"id":1048139,"name":"Rebecca Ronnen","orcid":null,"position":3,"is_corresponding":false},{"id":1491943,"name":"Sophie X. Song","orcid":"0009-0001-0559-4392","position":4,"is_corresponding":false},{"id":402724,"name":"Dimitris G. Placantonakis","orcid":"0000-0003-1950-2978","position":5,"is_corresponding":false},{"id":1492287,"name":"Jenna Richter","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:43.046112Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}