Journal article
ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling
S Schmidt, N Schumacher, J Schwarz, S Tangermann, L Kenner, M Schlederer, M Sibilia, M Linder, A Altendorf-Hofmann, T Knösel, ES Gruber, G Oberhuber, J Bolik, A Rehman, A Sinha, J Lokau, P Arnold, AS Cabron, F Zunke, C Becker-Pauly Show all
Journal of Experimental Medicine | ROCKEFELLER UNIV PRESS | Published : 2018
DOI: 10.1084/jem.20171696
Abstract
Colorectal 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 downregulation 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..
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Awarded by Horizon 2020 Framework Programme
Funding Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschaft, Bonn (CRC841, project C1 to D. Schmidt-Arras and S. Rose-John; CRC877, project A1 to S. Rose-John; SFB877, project A9 to C. Becker-Pauly; project A10 to C. Garbers; SFB877, project B9 to P. Rosenstiel; and the Cluster of Excellence "Inflammation at Interfaces"). The research of M. Sibilia was supported by Austrian Science Fund grant DK W1212 and the European Research Council Advanced Grant 694883.