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This study was designed to comprehensively assess adenosine metabolism in prostate and breast cancer cells. We identified cellular adenosine turnover as a complex cascade, comprising (1) the ectoenzymatic breakdown of ATP via sequential ecto-nucleotide pyrophosphatase\/phosphodiesterase-1 (NPP1, officially known as ENPP1), ecto-5\u2032-nucleotidase (CD73, also known as NT5E), and adenosine deaminase reactions, and ATP re-synthesis through a counteracting adenylate kinase and members of the nucleoside diphosphate kinase (NDPK, also known as NME\/NM23) family; (2) the uptake of nucleotide-derived adenosine via equilibrative nucleoside transporters; and (3) the intracellular adenosine phosphorylation into ATP by adenosine kinase and other nucleotide kinases. The exposure of cancer cells to 1% O2 for 24\u2005h triggered an \u223c2-fold upregulation of CD73, without affecting nucleoside transporters, adenosine kinase activity and cellular ATP content. The ability of adenosine to inhibit the tumor-initiating potential of breast cancer cells via a receptor-independent mechanism was confirmed in vivo using a xenograft mouse model. The existence of redundant pathways controlling extracellular and intracellular adenosine provides a sufficient justification for reexamination of the current concepts of cellular purine homeostasis and signaling in cancer.<\/jats:p>\n                  <jats:p>This article has an associated First Person interview with the first author of the paper.<\/jats:p>","DOI":"10.1242\/jcs.241463","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T13:49:25Z","timestamp":1587476965000},"source":"Crossref","is-referenced-by-count":43,"title":["Compartmentalization of adenosine metabolism in cancer cells and its modulation during acute hypoxia"],"prefix":"10.1242","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5396-7555","authenticated-orcid":false,"given":"Karolina","family":"Losenkova","sequence":"first","affiliation":[{"name":"MediCity Research Laboratory, University of Turku 1 , 20520 Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8485-9012","authenticated-orcid":false,"given":"Mariachiara","family":"Zuccarini","sequence":"additional","affiliation":[{"name":"MediCity Research Laboratory, University of Turku 1 , 20520 Turku , Finland"},{"name":"\u2018G. D'Annunzio\u2019 University of Chieti-Pescara 2 Department of Medical, Oral and Biotechnological Sciences , , 66100 Chieti , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marika","family":"Karikoski","sequence":"additional","affiliation":[{"name":"MediCity Research Laboratory, University of Turku 1 , 20520 Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Laurila","sequence":"additional","affiliation":[{"name":"MediCity Research Laboratory, University of Turku 1 , 20520 Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7740-5781","authenticated-orcid":false,"given":"Detlev","family":"Boison","sequence":"additional","affiliation":[{"name":"Robert Wood Johnson and New Jersey Medical Schools, Rutgers University 3 Department of Neurosurgery , , Piscataway , NJ 08854, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1922-9732","authenticated-orcid":false,"given":"Sirpa","family":"Jalkanen","sequence":"additional","affiliation":[{"name":"MediCity Research Laboratory, University of Turku 1 , 20520 Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6684-7982","authenticated-orcid":false,"given":"Gennady G.","family":"Yegutkin","sequence":"additional","affiliation":[{"name":"MediCity Research Laboratory, University of Turku 1 , 20520 Turku , Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,5,29]]},"reference":[{"key":"2024061318464505400_JCS241463C1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.imlet.2018.05.001","article-title":"Targeting the CD73-adenosine axis in immuno-oncology","volume":"205","author":"Allard","year":"2018","journal-title":"Immunol. 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