Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

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dc.citation.articleNumbere10250en_US
dc.citation.journalTitleeLifeen_US
dc.citation.volumeNumber5en_US
dc.contributor.authorZhao, Hongyunen_US
dc.contributor.authorYang, Lifengen_US
dc.contributor.authorBaddour, Joelleen_US
dc.contributor.authorAchreja, Abhinaven_US
dc.contributor.authorBernard, Vincenten_US
dc.contributor.authorMoss, Tyleren_US
dc.contributor.authorMarini, Juan C.en_US
dc.contributor.authorTudawe, Thavishaen_US
dc.contributor.authorSeviour, Elena G.en_US
dc.contributor.authorSan Lucas, F. Anthonyen_US
dc.contributor.authorAlvarez, Hectoren_US
dc.contributor.authorGupta, Sonalen_US
dc.contributor.authorMaiti, Sourindra N.en_US
dc.contributor.authorCooper, Laurenceen_US
dc.contributor.authorPeehl, Donnaen_US
dc.contributor.authorRam, Prahlad T.en_US
dc.contributor.authorMaitra, Anirbanen_US
dc.contributor.authorNagrath, Deepaken_US
dc.contributor.orgLaboratory for Systems Biology of Human Diseasesen_US
dc.date.accessioned2016-10-21T18:32:23Zen_US
dc.date.available2016-10-21T18:32:23Zen_US
dc.date.issued2016en_US
dc.description.abstractCancer-associated fibroblasts (CAFs) are a major cellular component of tumor microenvironment in most solid cancers. Altered cellular metabolism is a hallmark of cancer, and much of the published literature has focused on neoplastic cell-autonomous processes for these adaptations. We demonstrate that exosomes secreted by patient-derived CAFs can strikingly reprogram the metabolic machinery following their uptake by cancer cells. We find that CAF-derived exosomes (CDEs) inhibit mitochondrial oxidative phosphorylation, thereby increasing glycolysis and glutamine-dependent reductive carboxylation in cancer cells. Through 13C-labeled isotope labeling experiments we elucidate that exosomes supply amino acids to nutrient-deprived cancer cells in a mechanism similar to macropinocytosis, albeit without the previously described dependence on oncogenic-Kras signaling. Using intra-exosomal metabolomics, we provide compelling evidence that CDEs contain intact metabolites, including amino acids, lipids, and TCA-cycle intermediates that are avidly utilized by cancer cells for central carbon metabolism and promoting tumor growth under nutrient deprivation or nutrient stressed conditions.en_US
dc.identifier.citationZhao, Hongyun, Yang, Lifeng, Baddour, Joelle, et al.. "Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism." <i>eLife,</i> 5, (2016) eLife Sciences Publications Ltd.: http://dx.doi.org/10.7554/eLife.10250.en_US
dc.identifier.doihttp://dx.doi.org/10.7554/eLife.10250en_US
dc.identifier.urihttps://hdl.handle.net/1911/91992en_US
dc.language.isoengen_US
dc.publishereLife Sciences Publications Ltd.en_US
dc.rightsThis article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleTumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolismen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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