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dc.contributor.authorBian, Shu
dc.contributor.authorSun, Xiaofeng
dc.contributor.authorBai, Aiping
dc.contributor.authorZhang, Chunqing
dc.contributor.authorLi, Lingling
dc.contributor.authorEnjoji, Keiichi
dc.contributor.authorJunger, Wolfgang G
dc.contributor.authorRobson, Simon Christopher
dc.contributor.authorWu, Yan
dc.date.accessioned2013-10-17T18:21:06Z
dc.date.issued2013
dc.identifier.citationBian, Shu, Xiaofeng Sun, Aiping Bai, Chunqing Zhang, Linglin Li, Keiichi Enjyoji, Wolfgang G. Junger, Simon C. Robson, and Yan Wu. 2013. P2X7 integrates PI3K/AKT and AMPK-PRAS40-mTOR signaling pathways to mediate tumor cell death. PLoS ONE 8(4): e60184.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11181002
dc.description.abstractBackground: Extracellular adenosine triphosphate (ATP) functions as a novel danger signal that boosts antitumor immunity and can also directly kill tumor cells. We have previously reported that chronic exposure of tumor cells to ATP provokes P2X7-mediated tumor cell death, by as yet incompletely defined molecular mechanisms. Methodology/Principal Findings Here, we show that acute exposure of tumor cells to ATP results in rapid cytotoxic effects impacting several aspects of cell growth/survival, leading to inhibition of tumor growth in vitro and in vivo. Using agonist and antagonist studies together with generation of P2X7 deficient tumor cell lines by lentiviral shRNA delivery system, we confirm P2X7 to be the central control node transmitting extracellular ATP signals. We identify that downstream intracellular signaling regulatory networks implicate two signaling pathways: the known P2X7-PI3K/AKT axis and remarkably a novel P2X7-AMPK-PRAS40-mTOR axis. When exposed to high levels of extracellular ATP, these two signaling axes perturb the balance between growth and autophagy, thereby promoting tumor cell death. Conclusions: Our study defines novel molecular mechanisms underpinning the antitumor actions of P2X7 and provides a further rationale for purine-based drugs in targeted cancer therapy.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.pone.0060184en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3615040/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectMolecular Cell Biologyen_US
dc.subjectCell Deathen_US
dc.subjectCell Divisionen_US
dc.subjectCell Growthen_US
dc.subjectCellular Stress Responsesen_US
dc.subjectCytometryen_US
dc.subjectSignal Transductionen_US
dc.subjectMedicineen_US
dc.subjectOncologyen_US
dc.titleP2X7 Integrates PI3K/AKT and AMPK-PRAS40-mTOR Signaling Pathways to Mediate Tumor Cell Deathen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS ONEen_US
dash.depositing.authorWu, Yan
dc.date.available2013-10-17T18:21:06Z
dc.identifier.doi10.1371/journal.pone.0060184*
dash.authorsorderedfalse
dash.contributor.affiliatedBian, Shu
dash.contributor.affiliatedEnjoji, Keiichi
dash.contributor.affiliatedJunger, Wolfgang
dash.contributor.affiliatedLi, Lingling
dash.contributor.affiliatedWu, Yan
dash.contributor.affiliatedSun, X
dash.contributor.affiliatedBai, A
dash.contributor.affiliatedRobson, Simon


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