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This SASP comprises soluble factors and extracellular vesicles (EVs). Although soluble SASP components can induce senescence in neighboring cells, the specific contribution of EVs to paracrine senescence is poorly defined. Here, we show that EVs released by senescent tumor cells are necessary and sufficient to propagate senescence. Conditioned media from bleomycin\u2010induced senescent A549 cells triggered a growth arrest with morphological changes and upregulation of senescence markers in recipient tumor cells. Pharmacological inhibition of EV biogenesis using GW4869 or genetic downregulation of the EV secretion mediator RAB27A markedly attenuates paracrine senescence without affecting soluble SASP factor secretion or the senescent state of producer cells. Proteomic characterization reveals that senescent EVs exhibit a distinct molecular signature enriched for extracellular components and processes related to wound healing and hemostasis. Importantly, purified senescent EVs, devoid of soluble SASP factors, fully recapitulated paracrine senescence induction. These findings identify senescent EVs as key autonomous SASP effectors and highlight vesicular pathways as potential therapeutic targets in cancer and therapy\u2010induced senescence.<\/jats:p>","DOI":"10.1111\/acel.70722","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:57:24Z","timestamp":1790161044000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Extracellular Vesicles From Senescent Cancer Cells Are Necessary and Sufficient to Drive Paracrine Senescence"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4724-358X","authenticated-orcid":false,"given":"Valentin","family":"Estevez\u2010Souto","sequence":"first","affiliation":[{"name":"Laboratory of Cell Senescence, Cancer and Aging, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3653-2981","authenticated-orcid":false,"given":"Alex","family":"Miralles\u2010Dominguez","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Senescence, Cancer and Aging, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0362-2334","authenticated-orcid":false,"given":"Pablo","family":"Pedrosa","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Senescence, Cancer and Aging, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3572-0257","authenticated-orcid":false,"given":"Patricia","family":"Lado\u2010Fernandez","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Senescence, Cancer and Aging, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5802-6279","authenticated-orcid":false,"given":"Miguel A.","family":"Prados","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Senescence, Cancer and Aging, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1134-9138","authenticated-orcid":false,"given":"Alejandro","family":"Failde\u2010Fiestras","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Senescence, Cancer and Aging, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8134-6334","authenticated-orcid":false,"given":"Raquel","family":"Paredes\u2010Paredes","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Senescence, Cancer and Aging, Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela, Health Research Institute of Santiago de Compostela (IDIS)  Santiago de Compostela 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Technology, School of Pharmacy University of Santiago de Compostela  Santiago de Compostela Spain"},{"name":"Instituto Madrile\u00f1o de Estudios Avanzados en Nanociencia (IMDEA Nanociencia)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Migliavacca","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Center for Research in Biological Chemistry and Molecular Materials (CiQUS) University of Santiago de Compostela  Santiago de Compostela Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8870-5280","authenticated-orcid":false,"given":"Ester","family":"Polo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Center for Research in Biological Chemistry and Molecular Materials (CiQUS) University of Santiago de Compostela  Santiago de Compostela 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