The DOI matches its Crossref record; 41 of the 41 references it cites were found in a registry or an index.
Notch signaling regulates tumor angiogenesis by diverse mechanisms
Open accessAbstract
The Notch signaling pathway is fundamental to proper cardiovascular development and is now recognized as an important player in tumor angiogenesis. Two key Notch ligands have been implicated in tumor angiogenesis, Delta-like 4 and Jagged1. We introduce the proteins and how they work in normal developing vasculature and then discuss differing models describing the action of these Notch ligands in tumor angiogenesis. Endothelial Dll4 expression activates Notch resulting in restriction of new sprout development; for instance, in growing retinal vessels. In agreement with this activity, inhibition of Dll4-mediated Notch signaling in tumors results in hypersprouting of nonfunctional vasculature. This Dll4 inhibition may paradoxically lead to increased angiogenesis but poor tumor growth because the newly growing vessels are not functional. In contrast, Jagged1 has been described as a Notch ligand expressed in tumor cells that can have a positive influence on tumor angiogenesis, possibly by activating Notch on tumor endothelium. A novel Notch inhibitor, the Notch1 decoy, which blocks both Dll4 and Jagged1 has been recently shown to restrict tumor vessel growth. We discuss these models and speculate on therapeutic approaches.
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Cites
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VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia
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Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis
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Notch signaling is essential for vascular morphogenesis in mice
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Self-citationLessons from phase III clinical trials on anti-VEGF therapy for cancer
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Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis
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Breast cancer stem cells, cytokine networks, and the tumor microenvironment
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Role of Oncogenes and Tumor-suppressor Genes in Carcinogenesis: A Review
KONTOMANOLIS, E. N., KOUTRAS, A., SYLLAIOS, A., SCHIZAS, D., MASTORAKI, A., GARMPIS, N., DIAKOSAVVAS, M., ANGELOU, K., TSATSARIS, G., PAGKALOS, A., et al. (2020) · Anticancer Research · doi:10.21873/anticanres.14622 · Cited by 389
Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner
Pajvani, U. B., Shawber, C. J., Samuel, V. T., Birkenfeld, A. L., Shulman, G. I., Kitajewski, J., & Accili, D. (2011) · Nature Medicine · doi:10.1038/nm.2378 · Cited by 193
Self-citationTissue remodelling through branching morphogenesis
Affolter, M., Zeller, R., & Caussinus, E. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2797 · Cited by 185
Role of Notch signaling in colorectal cancer
Qiao, L., & Wong, B. C. Y. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp236 · Cited by 154
Metadata
- Authors
- Dufraine, J., Funahashi, Y., & Kitajewski, J.
- Venue
- Oncogene
- Published
- 2008-09-01
- Volume
- 27
- Issue
- 38
- Pages
- 5132-5137
- ISSN
- 0950-9232 (ISSN-L)
- 1476-5594
- OpenAlex
- W2054001958
- Cited by
- 277
- References
- 41
- FWCI
- 6.45
- Type
- journal article
- Language
- en
- Open access
- green
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