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dc.contributor.authorKoundouros, N
dc.contributor.authorKarali, E
dc.contributor.authorTripp, A
dc.contributor.authorValle, A
dc.contributor.authorInglese, P
dc.contributor.authorPerry, NJS
dc.contributor.authorMagee, DJ
dc.contributor.authorAnjomani Virmouni, S
dc.contributor.authorElder, GA
dc.contributor.authorTyson, AL
dc.contributor.authorDória, ML
dc.contributor.authorvan Weverwijk, A
dc.contributor.authorSoares, RF
dc.contributor.authorIsacke, CM
dc.contributor.authorNicholson, JK
dc.contributor.authorGlen, RC
dc.contributor.authorTakats, Z
dc.contributor.authorPoulogiannis, G
dc.date.accessioned2020-07-03T13:11:17Z
dc.date.issued2020-06-18
dc.identifier.citationCell, 2020, 181 (7), pp. 1596 - 1611.e27
dc.identifier.issn0092-8674
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3799
dc.identifier.eissn1097-4172
dc.identifier.doi10.1016/j.cell.2020.05.053
dc.description.abstractOncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making is largely unknown. Using the iKnife to sample the aerosol of cauterized specimens, we demonstrate a new mode of real-time diagnosis, coupling metabolic phenotype to mutant PIK3CA genotype. Oncogenic PIK3CA results in an increase in arachidonic acid and a concomitant overproduction of eicosanoids, acting to promote cell proliferation beyond a cell-autonomous manner. Mechanistically, mutant PIK3CA drives a multimodal signaling network involving mTORC2-PKCζ-mediated activation of the calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes with fatty acid-free diet to restore immunogenicity and selectively reduce mutant PIK3CA-induced tumorigenicity. Besides highlighting the potential for metabolic phenotyping in stratified medicine, this study reveals an important role for activated PI3K signaling in regulating arachidonic acid metabolism, uncovering a targetable metabolic vulnerability that largely depends on dietary fat restriction. VIDEO ABSTRACT.
dc.formatPrint-Electronic
dc.format.extent1596 - 1611.e27
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleMetabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids.
dc.typeJournal Article
dcterms.dateAccepted2020-05-28
rioxxterms.versionofrecord10.1016/j.cell.2020.05.053
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2020-06-18
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell
pubs.issue7
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Cell Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR/Students/PhD and MPhil/17/18 Starting Cohort
pubs.publication-statusPublished
pubs.volume181
pubs.embargo.termsNot known
icr.researchteamMolecular Cell Biologyen_US
icr.researchteamSignalling & Cancer Metabolismen_US
dc.contributor.icrauthorIsacke, Clare
dc.contributor.icrauthorPoulogiannis, Georgios
dc.contributor.icrauthorTripp, Aurelien
dc.contributor.icrauthorPerry, Nicholas


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