The DOI matches its Crossref record; 55 of the 55 references it cites were found in a registry or an index.
Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer
Open accessAbstract
Notch has been linked to β-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/β-catenin (down-regulated when blocking Wnt/β-catenin) that are directly regulated by Notch (repressed by γ-secretase inhibitors and up-regulated by active Notch1 in the absence of β-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through β-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/β-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC Min /+ with Jagged1 +/Δ mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear β-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by β-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.
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Cites
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The Roles of Cancer Stem Cells and Therapy Resistance in Colorectal Carcinoma
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Metadata
- Authors
- Rodilla, V., Villanueva, A., Obrador-Hevia, A., Robert-Moreno, À., Fernández-Majada, V., Grilli, A., López-Bigas, N., Bellora, N., Albà, M. M., Torres, F., Duñach, M., Sanjuan, X., Gonzalez, S., Gridley, T., Capella, G., Bigas, A., & Espinosa, L.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2009-04-14
- Volume
- 106
- Issue
- 15
- Pages
- 6315-6320
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2062150443
- Cited by
- 384
- References
- 55
- FWCI
- 11.88
- Type
- journal article
- Language
- en
- Open access
- green
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- Rodilla, V., Villanueva, A., Obrador-Hevia, A., Robert-Moreno, À., Fernández-Majada, V., Grilli, A., López-Bigas, N., Bellora, N., Albà, M. M., Torres, F., Duñach, M., Sanjuan, X., Gonzalez, S., Gridley, T., Capella, G., Bigas, A., & Espinosa, L. (2009). Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0813221106
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
