dc.contributor.author | Koundouros, N | |
dc.contributor.author | Karali, E | |
dc.contributor.author | Tripp, A | |
dc.contributor.author | Valle, A | |
dc.contributor.author | Inglese, P | |
dc.contributor.author | Perry, NJS | |
dc.contributor.author | Magee, DJ | |
dc.contributor.author | Anjomani Virmouni, S | |
dc.contributor.author | Elder, GA | |
dc.contributor.author | Tyson, AL | |
dc.contributor.author | Dória, ML | |
dc.contributor.author | van Weverwijk, A | |
dc.contributor.author | Soares, RF | |
dc.contributor.author | Isacke, CM | |
dc.contributor.author | Nicholson, JK | |
dc.contributor.author | Glen, RC | |
dc.contributor.author | Takats, Z | |
dc.contributor.author | Poulogiannis, G | |
dc.date.accessioned | 2020-07-03T13:11:17Z | |
dc.date.issued | 2020-06-25 | |
dc.identifier.citation | Cell, 2020, 181 (7), pp. 1596 - 1611.e27 | |
dc.identifier.issn | 0092-8674 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3799 | |
dc.identifier.eissn | 1097-4172 | |
dc.identifier.doi | 10.1016/j.cell.2020.05.053 | |
dc.description.abstract | Oncogenic 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.format | Print-Electronic | |
dc.format.extent | 1596 - 1611.e27 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | CELL PRESS | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2020-05-28 | |
rioxxterms.versionofrecord | 10.1016/j.cell.2020.05.053 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by-nc-nd/4.0 | |
rioxxterms.licenseref.startdate | 2020-06-18 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cell | |
pubs.issue | 7 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 181 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Cell Biology | |
icr.researchteam | Signalling & Cancer Metabolism | |
dc.contributor.icrauthor | Koundouros, Nikolaos | |
dc.contributor.icrauthor | Tripp, Aurelien | |
dc.contributor.icrauthor | Perry, Nicholas | |
dc.contributor.icrauthor | Isacke, Clare | |
dc.contributor.icrauthor | Poulogiannis, Georgios | |