{"doi":"10.3390/ijms26094286","title":"Disruption of P2Y2 Signaling Promotes Breast Tumor Cell Dissemination by Reducing ATP-Dependent Calcium Elevation and Actin Localization to Cell Junctions","abstract":"The tumor microenvironment and healing wounds both contain extremely high concentrations of adenosine triphosphate (ATP) compared to normal tissue. The P2Y2 receptor, an ATP-activated purinergic receptor, is typically associated with pulmonary, endothelial, and neurological cell signaling. Here, we examine ATP-dependent signaling in breast epithelial cells and how it is altered in metastatic breast cancer. Using rapid imaging techniques, we show how ATP-activated P2Y2 signaling causes an increase in intracellular Ca2+ in non-tumorigenic breast epithelial cells, approximately 3-fold higher than their tumorigenic and metastatic counterparts. The non-tumorigenic cells respond to increased Ca2+ with actin polymerization and localization to the cell edges after phalloidin staining, while the metastatic cells remain unaffected. The increase in intracellular Ca2+ after ATP stimulation was blunted to control levels using a P2Y2 antagonist, which also prevented actin mobilization and significantly increased cell dissemination from spheroids in non-tumorigenic cells. Furthermore, the lack of Ca2+ changes and actin mobilization in metastatic breast cancer cells could be due to the reduced P2Y2 expression, which correlates with poorer overall survival in breast cancer patients. This study elucidates the rapid changes that occur after elevated intracellular Ca2+ in breast epithelial cells and how metastatic cancer cells have adapted to evade this cellular response.","journal":"International Journal of Molecular Sciences","year":2025,"id":532324,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9576,"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":354693,"name":"Stephen J. P. Pratt","orcid":null,"position":1,"is_corresponding":false},{"id":383960,"name":"Keyata N. Thompson","orcid":"0000-0002-8097-9014","position":2,"is_corresponding":false},{"id":481492,"name":"David A. Annis","orcid":"0000-0001-6167-5819","position":3,"is_corresponding":false},{"id":257945,"name":"Rachel Lee","orcid":"0000-0001-9359-0422","position":4,"is_corresponding":false},{"id":335116,"name":"Julia A. Ju","orcid":"0000-0002-6395-4501","position":5,"is_corresponding":false},{"id":1129228,"name":"Darin E. Gilchrist","orcid":"0000-0001-5883-4989","position":6,"is_corresponding":false},{"id":946940,"name":"Megan B. Stemberger","orcid":"0000-0003-2712-5455","position":7,"is_corresponding":false},{"id":463236,"name":"Liron Boyman","orcid":"0000-0002-4485-680X","position":8,"is_corresponding":false},{"id":443912,"name":"W. Jonathan Lederer","orcid":"0000-0002-8488-2180","position":9,"is_corresponding":false},{"id":288411,"name":"Michele Vítolo","orcid":"0000-0001-8055-9645","position":10,"is_corresponding":false},{"id":288412,"name":"Stuart S. Martin","orcid":"0000-0002-4378-4381","position":11,"is_corresponding":false},{"id":946939,"name":"Makenzy L. Mull","orcid":"0000-0002-6029-232X","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T02:51:23.237536Z","pmid":"40362524","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":[]}