403 Tissue-Specific Induction of Activating Transcription Factor 6 Signaling Promotes Intestinal Dysbiosis and Colonic Tumorigenesis

The activating transcription factor 6 (ATF6) is one of the major transducers of the endoplasmic reticulum unfolded protein response (ER UPR). To study how ATF6 signaling affects intestinal epithelial cells (IEC) and intestinal health, nATF6 IEC mice were investigated. These mice express the activated form of ATF6 (nATF6) specifically in IEC. The dissertation shows that nATF6 expression in IEC promotes tumorigenesis in the large intestine which is linked to dysbiosis of the intestinal microbiota. The nATF6 IEC model and the analysis of ATF6 in colon cancer patients provide evidence for a contribution of ATF6 signaling to the pathogenesis of intestinal cancer.