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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Bibliographic Details
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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Summary: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.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11040555