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Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis

Proliferation and differentiation of intestinal epithelial cells is assisted by highly specialized and well-regulated signaling cascades. The Wnt pathway, which is one of the fundamental pathways in the intestine, contributes to the organization of proliferative intestinal crypts by positioning and...

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Published in:	Cancers 2019-04, Vol.11 (4), p.555
Main Authors:	Kaemmerer, Elke, Jeon, Min Kyung, Berndt, Alexander, Liedtke, Christian, Gassler, Nikolaus
Format:	Article
Language:	English
Subjects:	Carcinogenesis Caspase-8 Cell death Cell differentiation Cell fate Cell proliferation Epithelial cells Fatty acids Generic drugs Genes Goblet cells Homeostasis Intestine Kinases Mutation Physiology Progenitor cells Proteins Review Signal transduction Stem cells Tumorigenesis Tumors Villus Wnt protein
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container_title	Cancers
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creator	Kaemmerer, Elke Jeon, Min Kyung Berndt, Alexander Liedtke, Christian Gassler, Nikolaus
description	Proliferation and differentiation of intestinal epithelial cells is assisted by highly specialized and well-regulated signaling cascades. The Wnt pathway, which is one of the fundamental pathways in the intestine, contributes to the organization of proliferative intestinal crypts by positioning and cycling of intestinal stem cells and their derivatives. The Wnt pathway promotes differentiation of intestinal secretory cell types along the crypt-plateau and crypt-villus axis. In contrast to the Wnt pathway, the intestinal Notch cascade participates in cellular differentiation and directs progenitor cells towards an absorptive fate with diminished numbers of Paneth and goblet cells. Opposing activities of Notch and Wnt signaling in the regulation of intestinal stem cells and the enterocytic cell fate have been elucidated recently. In fact, targeting Notch was able to overcome tumorigenesis of intestinal adenomas, prevented carcinogenesis, and counteracted Paneth cell death in the absence of caspase 8. At present, pharmacological Notch inhibition is considered as an interesting tool targeting the intrinsic Wnt pathway activities in intestinal non-neoplastic disease and carcinogenesis.
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subjects	Carcinogenesis Caspase-8 Cell death Cell differentiation Cell fate Cell proliferation Epithelial cells Fatty acids Generic drugs Genes Goblet cells Homeostasis Intestine Kinases Mutation Physiology Progenitor cells Proteins Review Signal transduction Stem cells Tumorigenesis Tumors Villus Wnt protein
title	Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis
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