Maintenance and disruption of intestinal epithelial homeostasis

In this thesis the role of ER stress on the intestinal epithelial stem cell state in the context of colorectal cancer has been explored using different in vivo and in vitro genetically modified experimental models. Inactivation of APC is an early and key event in the development of colorectal cancer. This has attracted researchers to develop drugs that target molecules specific to APC-mutated cells. One of the main findings presented in this thesis is that ER stress reduces adenoma formation in the Apc-mutated mouse intestine. In addition, a deeper understanding of the underlying mechanism responsible for ER stress-induced loss of stemness is provided by identifying transcription factors altered upon ER stress. Furthermore, our ATF2 and ATF7 experiments demonstrate an uncoupling role of the ATF proteins in health and disease, a concept that provides key opportunities for the development of targeted therapies.