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dc.contributor.authorTape, C
dc.contributor.authorLing, S
dc.contributor.authorDimitriadi, M
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, G
dc.contributor.authorLauffenburger, D
dc.contributor.authorJørgensen, Claus
dc.date.accessioned2016-05-25T15:23:17Zen
dc.date.available2016-05-25T15:23:17Zen
dc.date.issued2016-05-05en
dc.identifier.citationOncogenic KRAS regulates tumor cell signaling via stromal reciprocation. 2016, 165 (4):910-20 Cellen
dc.identifier.issn1097-4172en
dc.identifier.pmid27087446en
dc.identifier.doi10.1016/j.cell.2016.03.029en
dc.identifier.urihttp://hdl.handle.net/10541/610741en
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.language.isoenen
dc.rightsArchived with thanks to Cellen
dc.titleOncogenic KRAS regulates tumor cell signaling via stromal reciprocation.en
dc.typeArticleen
dc.contributor.departmentThe Institute ofCancer Research, 237 Fulham Road, London SW3 6JB,en
dc.identifier.journalCellen
html.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.


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