ADAM17 is required for EGF-R-induced intestinal tumors via IL-6 trans-signaling.

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 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

SUBMITTER: Schmidt S 

PROVIDER: S-EPMC5881468 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature