Turning it down a Notch | Nature Reviews Cancer

Access through your institution Buy or subscribe Kitajewski and colleagues generated a soluble form of the NOTCH1 receptor (NOTCH1 decoy) that efficiently attenuated activation of NOTCH1 by

its ligands jagged 1, delta-like 1 (DLL1) and DLL4, making it a pan-ligand inhibitor and a valuable tool with which to further study the role of NOTCH1 signalling in angiogenesis. The

authors first examined the requirement for NOTCH1 in physiological angiogenesis and implanted a chamber containing VEGF121-producing tumour cells under the dorsal skin of a mouse.

Angiogenesis induced in the smooth muscle layer overlying the chamber was significantly reduced by coexpression of NOTCH1 decoy, suggesting that dermal angiogenesis requires NOTCH1 receptor

activation. The authors also observed that murine mammary tumour cells producing fibroblast growth factor 4 showed increased expression of jagged 1 and, based on this, they predicted that

tumours arising from these cells would require NOTCH1 for growth and angiogenesis. Indeed, NOTCH1 decoy expression in these cells led to a significant reduction in tumour volume following

subcutaneous implantation in mice. Furthermore, immunostaining and real-time PCR experiments confirmed a substantial decrease in both NOTCH1 signalling and tumour angiogenesis in NOTCH1

decoy-expressing tumours. This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal Receive 12 print

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PAPER * Funahashi, Y. et al. A Notch1 ectodomain construct inhibits endothelial Notch signaling, tumour growth and angiogenesis. _Cancer Res._ 68, 4727–4735 (2008) Article  CAS  Google

Scholar  Download references Authors * Safia Ali Danovi View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions

ABOUT THIS ARTICLE CITE THIS ARTICLE Danovi, S. Turning it down a Notch. _Nat Rev Cancer_ 8, 573 (2008). https://doi.org/10.1038/nrc2450 Download citation * Published: 17 July 2008 * Issue

Date: August 2008 * DOI: https://doi.org/10.1038/nrc2450 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable

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