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dc.contributor.authorTape, Christopher J.
dc.contributor.authorLing, Stephanie
dc.contributor.authorDimitriadi, Maria
dc.contributor.authorMcMahon, Kelly M.
dc.contributor.authorWorboys, Jonathan D.
dc.contributor.authorLeong, Hui Sun
dc.contributor.authorNorrie, Ida C.
dc.contributor.authorMiller, Crispin J.
dc.contributor.authorPoulogiannis, George
dc.contributor.authorLauffenburger, Douglas A.
dc.contributor.authorJørgensen, Claus
dc.date.accessioned2017-01-23T18:37:22Z
dc.date.available2017-01-23T18:37:22Z
dc.date.issued2016-05-05
dc.identifier.citationTape , C J , Ling , S , Dimitriadi , M , McMahon , K M , Worboys , J D , Leong , H S , Norrie , I C , Miller , C J , Poulogiannis , G , Lauffenburger , D A & Jørgensen , C 2016 , ' Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation ' , Cell , vol. 165 , no. 4 , pp. 910-920 . https://doi.org/10.1016/j.cell.2016.03.029
dc.identifier.issn0092-8674
dc.identifier.otherPURE: 10103412
dc.identifier.otherPURE UUID: 60dc8410-4bc5-4bd7-b59d-ec930d3abb72
dc.identifier.otherPubMed: 27087446
dc.identifier.otherScopus: 84963502839
dc.identifier.urihttp://hdl.handle.net/2299/17539
dc.descriptionThis is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Open Access funded by Wellcome Trust. Tape et al., Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation, Cell 165, 1-11,( May 5, 2016), copyright 2016 The Authors, http://dx.doi.org/10.1016/j.cell.2016.03.029.
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.en
dc.format.extent11
dc.language.isoeng
dc.relation.ispartofCell
dc.rightsOpen
dc.titleOncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocationen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionDepartment of Biological and Environmental Sciences
dc.contributor.institutionGeography, Environment and Agriculture
dc.contributor.institutionBiosciences Research Group
dc.contributor.institutionWeight and Obesity Research Group
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
dc.description.versiontypeFinal Published version
dcterms.dateAccepted2016-05-05
rioxxterms.versionVoR
rioxxterms.versionofrecordhttps://doi.org/10.1016/j.cell.2016.03.029
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
rioxxterms.typeJournal Article/Review
herts.preservation.rarelyaccessedtrue
herts.rights.accesstypeOpen


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