Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism

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dc.citation.articleNumbere10250
dc.citation.journalTitleeLife
dc.citation.volumeNumber5
dc.contributor.authorZhao, Hongyun
dc.contributor.authorYang, Lifeng
dc.contributor.authorBaddour, Joelle
dc.contributor.authorAchreja, Abhinav
dc.contributor.authorBernard, Vincent
dc.contributor.authorMoss, Tyler
dc.contributor.authorMarini, Juan C.
dc.contributor.authorTudawe, Thavisha
dc.contributor.authorSeviour, Elena G.
dc.contributor.authorSan Lucas, F. Anthony
dc.contributor.authorAlvarez, Hector
dc.contributor.authorGupta, Sonal
dc.contributor.authorMaiti, Sourindra N.
dc.contributor.authorCooper, Laurence
dc.contributor.authorPeehl, Donna
dc.contributor.authorRam, Prahlad T.
dc.contributor.authorMaitra, Anirban
dc.contributor.authorNagrath, Deepak
dc.contributor.orgLaboratory for Systems Biology of Human Diseases
dc.date.accessioned2016-10-21T18:32:23Z
dc.date.available2016-10-21T18:32:23Z
dc.date.issued2016
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.
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.
dc.identifier.doihttp://dx.doi.org/10.7554/eLife.10250
dc.identifier.urihttps://hdl.handle.net/1911/91992
dc.language.isoeng
dc.publishereLife Sciences Publications Ltd.
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.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleTumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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