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dc.contributor.authorSchmidt, S
dc.contributor.authorSchumacher, N
dc.contributor.authorSchwarz, J
dc.contributor.authorTangermann, S
dc.contributor.authorKenner, L
dc.contributor.authorSchlederer, M
dc.contributor.authorSibilia, M
dc.contributor.authorLinder, M
dc.contributor.authorAltendorf-Hofmann, A
dc.contributor.authorKnoesel, T
dc.contributor.authorGruber, ES
dc.contributor.authorOberhuber, G
dc.contributor.authorBolik, J
dc.contributor.authorRehman, A
dc.contributor.authorSinha, A
dc.contributor.authorLokau, J
dc.contributor.authorArnold, P
dc.contributor.authorCabron, A-S
dc.contributor.authorZunke, F
dc.contributor.authorBecker-Pauly, C
dc.contributor.authorPreaudet, A
dc.contributor.authorNguyen, P
dc.contributor.authorHuynh, J
dc.contributor.authorAfshar-Sterle, S
dc.contributor.authorChand, AL
dc.contributor.authorWestermann, J
dc.contributor.authorDempsey, PJ
dc.contributor.authorGarbers, C
dc.contributor.authorSchmidt-Arras, D
dc.contributor.authorRosenstiel, P
dc.contributor.authorPutoczki, T
dc.contributor.authorErnst, M
dc.contributor.authorRose-John, S
dc.date.accessioned2020-12-17T03:13:02Z
dc.date.available2020-12-17T03:13:02Z
dc.date.issued2018-04-01
dc.identifierpii: jem.20171696
dc.identifier.citationSchmidt, S., Schumacher, N., Schwarz, J., Tangermann, S., Kenner, L., Schlederer, M., Sibilia, M., Linder, M., Altendorf-Hofmann, A., Knoesel, T., Gruber, E. S., Oberhuber, G., Bolik, J., Rehman, A., Sinha, A., Lokau, J., Arnold, P., Cabron, A. -S., Zunke, F. ,... Rose-John, S. (2018). ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling. JOURNAL OF EXPERIMENTAL MEDICINE, 215 (4), pp.1205-1225. https://doi.org/10.1084/jem.20171696.
dc.identifier.issn0022-1007
dc.identifier.urihttp://hdl.handle.net/11343/254793
dc.description.abstractColorectal cancer is treated with antibodies blocking epidermal growth factor receptor (EGF-R), but therapeutic success is limited. EGF-R is stimulated by soluble ligands, which are derived from transmembrane precursors by ADAM17-mediated proteolytic cleavage. In mouse intestinal cancer models in the absence of ADAM17, tumorigenesis was almost completely inhibited, and the few remaining tumors were of low-grade dysplasia. RNA sequencing analysis demonstrated down-regulation of STAT3 and Wnt pathway components. Because EGF-R on myeloid cells, but not on intestinal epithelial cells, is required for intestinal cancer and because IL-6 is induced via EGF-R stimulation, we analyzed the role of IL-6 signaling. Tumor formation was equally impaired in IL-6-/- mice and sgp130Fc transgenic mice, in which only trans-signaling via soluble IL-6R is abrogated. ADAM17 is needed for EGF-R-mediated induction of IL-6 synthesis, which via IL-6 trans-signaling induces β-catenin-dependent tumorigenesis. Our data reveal the possibility of a novel strategy for treatment of colorectal cancer that could circumvent intrinsic and acquired resistance to EGF-R blockade.
dc.languageEnglish
dc.publisherROCKEFELLER UNIV PRESS
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0
dc.titleADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling
dc.typeJournal Article
dc.identifier.doi10.1084/jem.20171696
melbourne.affiliation.departmentSurgery (RMH)
melbourne.affiliation.departmentClinical Pathology
melbourne.source.titleJournal of Experimental Medicine
melbourne.source.volume215
melbourne.source.issue4
melbourne.source.pages1205-1225
dc.rights.licenseCC BY-NC-SA
melbourne.elementsid1321535
melbourne.contributor.authorPutoczki, Tracy
melbourne.contributor.authorErnst, Matthias
melbourne.contributor.authorNguyen, Paul
dc.identifier.eissn1540-9538
melbourne.accessrightsOpen Access


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