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dc.contributor.authorTape, CJ
dc.contributor.authorLing, S
dc.contributor.authorDimitriadi, M
dc.contributor.authorMcMahon, KM
dc.contributor.authorWorboys, JD
dc.contributor.authorLeong, HS
dc.contributor.authorNorrie, IC
dc.contributor.authorMiller, CJ
dc.contributor.authorPoulogiannis, G
dc.contributor.authorLauffenburger, DA
dc.contributor.authorJørgensen, C
dc.date.accessioned2016-10-26T16:38:36Z
dc.date.issued2016-06-16
dc.identifier.citationCell, 2016, 165 (7), pp. 1818 - ?
dc.identifier.issn0092-8674
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/191
dc.identifier.eissn1097-4172
dc.identifier.doi10.1016/j.cell.2016.05.079
dc.description.abstractOncogenic mutations regulate signaling within both tumor cells and adjacent stromal cells. Here, we show that oncogenic KRAS (KRAS(G12D)) also regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with multivariate phosphoproteomics, we analyzed heterocellular KRAS(G12D) signaling in pancreatic ductal adenocarcinoma (PDA) cells. Tumor cell KRAS(G12D) engages heterotypic fibroblasts, which subsequently instigate reciprocal signaling in the tumor cells. Reciprocal signaling employs additional kinases and doubles the number of regulated signaling nodes from cell-autonomous KRAS(G12D). Consequently, reciprocal KRAS(G12D) produces a tumor cell phosphoproteome and total proteome that is distinct from cell-autonomous KRAS(G12D) alone. Reciprocal signaling regulates tumor cell proliferation and apoptosis and increases mitochondrial capacity via an IGF1R/AXL-AKT axis. These results demonstrate that oncogene signaling should be viewed as a heterocellular process and that our existing cell-autonomous perspective underrepresents the extent of oncogene signaling in cancer. VIDEO ABSTRACT.
dc.formatPrint
dc.format.extent1818 - ?
dc.languageeng
dc.language.isoeng
dc.publisherCELL PRESS
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleOncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation.
dc.typeJournal Article
dcterms.dateAccepted2016-03-17
rioxxterms.versionofrecord10.1016/j.cell.2016.05.079
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2016-06
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCell
pubs.issue7
pubs.notesNo embargo
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/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Cell Communication
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Oncogene
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/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Signalling & Cancer Metabolism
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Cell Communication
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Closed research teams/Oncogene
pubs.publication-statusPublished
pubs.volume165
pubs.embargo.termsNo embargo
icr.researchteamSignalling & Cancer Metabolism
icr.researchteamCell Communication
icr.researchteamOncogene
dc.contributor.icrauthorWorboys, Jonathan David
dc.contributor.icrauthorPoulogiannis, Georgios


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