Toby J Phesse, Michael Buchert, Emma Stuart, Dustin J Flanagan, Maree Faux, Shoukat Afshar-Sterle, Francesca Walker, Hui-Hua Zhang, Cameron J Nowell, Robert Jorissen, Chin Wee Tan, Yumiko Hirokawa, Moritz F Eissmann, Ashleigh R Poh, Jordane Malaterre, Helen B Pearson, David G Kirsch, Paolo Provero, Valeria Poli, Robert G Ramsay, Oliver Sieber, Antony W Burgess, Dennis Huszar, Elizabeth Vincan, Matthias Ernst
Most colon cancers arise from somatic mutations in the tumor suppressor gene APC (adenomatous polyposis coli), and these mutations cause constitutive activation of the Wnt-to-β-catenin pathway in the intestinal epithelium. Because Wnt-β-catenin signaling is required for homeostasis and regeneration of the adult intestinal epithelium, therapeutic targeting of this pathway is challenging. We found that genetic activation of the cytokine-stimulated pathway mediated by the receptor gp130, the associated Jak (Janus kinase) kinases, and the transcription factor Stat3 (signal transducer and activator of transcription 3) was required for intestinal regeneration in response to irradiation-induced damage in wild-type mice and for tumorigenesis in Apc-mutant mice...
September 30, 2014: Science Signaling