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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-04-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/11/4/555 |
| _version_ | 1797714038845603840 |
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| author | Elke Kaemmerer Min Kyung Jeon Alexander Berndt Christian Liedtke Nikolaus Gassler |
| author_facet | Elke Kaemmerer Min Kyung Jeon Alexander Berndt Christian Liedtke Nikolaus Gassler |
| author_sort | Elke Kaemmerer |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-12T07:46:05Z |
| format | Article |
| id | doaj.art-acde719be9e04fcb848fc040cc36b347 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T07:46:05Z |
| publishDate | 2019-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-acde719be9e04fcb848fc040cc36b3472023-09-02T21:02:07ZengMDPI AGCancers2072-66942019-04-0111455510.3390/cancers11040555cancers11040555Targeting Wnt Signaling via Notch in Intestinal CarcinogenesisElke Kaemmerer0Min Kyung Jeon1Alexander Berndt2Christian Liedtke3Nikolaus Gassler4Institute of Pathology, RWTH Aachen University, 52074 Aachen, GermanyDivision of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul 03722, KoreaSection Pathology, Institute of Legal Medicine, University Hospital Jena, 07747 Jena, GermanyDepartment of Medicine III, RWTH Aachen University, 52074 Aachen, GermanyInstitute of Pathology, RWTH Aachen University, 52074 Aachen, GermanyProliferation 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.https://www.mdpi.com/2072-6694/11/4/555cancercaspase 8intestinelncRNANotchtargetingWnt |
| spellingShingle | Elke Kaemmerer Min Kyung Jeon Alexander Berndt Christian Liedtke Nikolaus Gassler Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis Cancers cancer caspase 8 intestine lncRNA Notch targeting Wnt |
| title | Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis |
| title_full | Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis |
| title_fullStr | Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis |
| title_full_unstemmed | Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis |
| title_short | Targeting Wnt Signaling via Notch in Intestinal Carcinogenesis |
| title_sort | targeting wnt signaling via notch in intestinal carcinogenesis |
| topic | cancer caspase 8 intestine lncRNA Notch targeting Wnt |
| url | https://www.mdpi.com/2072-6694/11/4/555 |
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