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dc.contributor.authorKamphorst, J. J.
dc.contributor.authorNofal, M.
dc.contributor.authorCommisso, C.
dc.contributor.authorHackett, S. R.
dc.contributor.authorLu, W.
dc.contributor.authorGrabocka, E.
dc.contributor.authorMiller, G.
dc.contributor.authorDrebin, J. A.
dc.contributor.authorBar-Sagi, D.
dc.contributor.authorThompson, C. B.
dc.contributor.authorRabinowitz, J. D.
dc.contributor.authorVander Heiden, Matthew G.
dc.date.accessioned2016-12-14T21:07:35Z
dc.date.available2016-12-14T21:07:35Z
dc.date.issued2015-02
dc.identifier.issn0008-5472
dc.identifier.issn1538-7445
dc.identifier.urihttp://hdl.handle.net/1721.1/105821
dc.description.abstractGlucose and amino acids are key nutrients supporting cell growth. Amino acids are imported as monomers, but an alternative route induced by oncogenic KRAS involves uptake of extracellular proteins via macropinocytosis and subsequent lysosomal degradation of these proteins as a source of amino acids. In this study, we examined the metabolism of pancreatic ductal adenocarcinoma (PDAC), a poorly vascularized lethal KRAS-driven malignancy. Metabolomic comparisons of human PDAC and benign adjacent tissue revealed that tumor tissue was low in glucose, upper glycolytic intermediates, creatine phosphate, and the amino acids glutamine and serine, two major metabolic substrates. Surprisingly, PDAC accumulated essential amino acids. Such accumulation could arise from extracellular proteins being degraded through macropinocytosis in quantities necessary to meet glutamine requirements, which in turn produces excess of most other amino acids. Consistent with this hypothesis, active macropinocytosis is observed in primary human PDAC specimens. Moreover, in the presence of physiologic albumin, we found that cultured murine PDAC cells grow indefinitely in media lacking single essential amino acids and replicate once in the absence of free amino acids. Growth under these conditions was characterized by simultaneous glutamine depletion and essential amino acid accumulation. Overall, our findings argue that the scavenging of extracellular proteins is an important mode of nutrient uptake in PDACen_US
dc.description.sponsorshipStand Up To Cancer (Dream Team Translational Research Grant SU2C-AACR-DT0509)en_US
dc.language.isoen_US
dc.publisherAmerican Association for Cancer Researchen_US
dc.relation.isversionofhttp://dx.doi.org/10.1158/0008-5472.can-14-2211en_US
dc.rightsCreative Commons Attribution-Noncommercial-Share Alikeen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/en_US
dc.sourcePMCen_US
dc.titleHuman Pancreatic Cancer Tumors Are Nutrient Poor and Tumor Cells Actively Scavenge Extracellular Proteinen_US
dc.typeArticleen_US
dc.identifier.citationKamphorst, J. J. et al. “Human Pancreatic Cancer Tumors Are Nutrient Poor and Tumor Cells Actively Scavenge Extracellular Protein.” Cancer Research 75.3 (2015): 544–553.en_US
dc.contributor.departmentDavid H. Koch Institute for Integrative Cancer Research at MITen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorVander Heiden, Matthew G.
dc.relation.journalCancer Researchen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsKamphorst, J. J.; Nofal, M.; Commisso, C.; Hackett, S. R.; Lu, W.; Grabocka, E.; Vander Heiden, M. G.; Miller, G.; Drebin, J. A.; Bar-Sagi, D.; Thompson, C. B.; Rabinowitz, J. D.en_US
dspace.embargo.termsNen_US
dc.identifier.orcidhttps://orcid.org/0000-0002-6702-4192
mit.licenseOPEN_ACCESS_POLICYen_US


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