{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T04:45:26Z","timestamp":1782794726027,"version":"3.54.5"},"reference-count":68,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T00:00:00Z","timestamp":1754438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)","award":["11230446"],"award-info":[{"award-number":["11230446"]}]},{"name":"Agencia Nacional de Investigaci\u00f3n y Desarrollo (ANID)","award":["1212026"],"award-info":[{"award-number":["1212026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Gastric cancer (GC) is among the most common and deadliest types of cancer, with a poor prognosis primarily due to late-stage detection and the presence of cancer stem cells (CSCs). This study investigates the mechanisms regulating extracellular adenosine levels in gastric cancer stem-like cells (GCSCs) derived from the MKN-74 cell line. Our results show that GCSCs release more ATP into the extracellular medium and exhibit higher levels of CD39 expression, which enables them to hydrolyze a greater amount of ATP. Furthermore, we also found that GCSCs possess a greater capacity to hydrolyze AMP, primarily due to the activity of the CD73 protein, with no significant changes in CD73 transcripts and protein levels between GCSCs and differentiated cells. Additionally, adenosine transport is primarily mediated by members of the equilibrative nucleoside transporter (ENT) family in GCSCs, where a significant increase in the expression level of the ENT2 protein is observed compared to non-GCSCs MKN-74 cells. These findings suggest that targeting the adenosine metabolism pathway in GCSCs could be a potential therapeutic strategy for gastric cancer.<\/jats:p>","DOI":"10.3390\/ijms26157594","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T10:13:51Z","timestamp":1754475231000},"page":"7594","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Extracellular Adenosine in Gastric Cancer: The Role of GCSCs"],"prefix":"10.3390","volume":"26","author":[{"given":"Sharin","family":"Valdivia","sequence":"first","affiliation":[{"name":"Cancer Biology Laboratory, Facultad de Medicina, Universidad San Sebasti\u00e1n, Sede Concepci\u00f3n, Campus Tres Pascualas, Concepci\u00f3n 4080871, Chile"},{"name":"Departamento de Ciencias Biol\u00f3gicas y Qu\u00edmicas, Facultad de Ciencias, Universidad San Sebasti\u00e1n, Sede Concepci\u00f3n, Campus Tres Pascualas, Concepci\u00f3n 4080871, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1311-9492","authenticated-orcid":false,"given":"Carolina","family":"A\u00f1azco","sequence":"additional","affiliation":[{"name":"Nutritional Biochemistry Laboratory, School of Nutrition and Dietetics, Faculty of Rehabilitation and Quality of Life Sciences, San Sebastian University, Valdivia 5091000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camila","family":"Riquelme","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Facultad de Medicina, Universidad San Sebasti\u00e1n, Sede Concepci\u00f3n, Campus Tres Pascualas, Concepci\u00f3n 4080871, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Constanza","family":"Carrasco","sequence":"additional","affiliation":[{"name":"Escuela de Medicina, Facultad de Medicina, Universidad San Sebasti\u00e1n, Sede Concepci\u00f3n, Campus Tres Pascualas, Concepci\u00f3n 4080871, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Cancer Biology Laboratory, Facultad de Medicina, Universidad San Sebasti\u00e1n, Sede Concepci\u00f3n, Campus Tres Pascualas, Concepci\u00f3n 4080871, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8413-8028","authenticated-orcid":false,"given":"Sebasti\u00e1n","family":"Alarc\u00f3n","sequence":"additional","affiliation":[{"name":"Cancer Biology Laboratory, Facultad de Medicina, Universidad San Sebasti\u00e1n, Sede Concepci\u00f3n, Campus Tres Pascualas, Concepci\u00f3n 4080871, Chile"},{"name":"Escuela de Medicina, Facultad de Medicina, Universidad San Sebasti\u00e1n, Sede Concepci\u00f3n, Campus Tres Pascualas, Concepci\u00f3n 4080871, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s11523-024-01097-2","article-title":"Diffuse Gastric Cancer: A Comprehensive Review of Molecular Features and Emerging Therapeutics","volume":"19","author":"Wu","year":"2024","journal-title":"Target. 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