| First Author | Lin S | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 16074 | PubMed ID | 28719575 |
| Mgi Jnum | J:249947 | Mgi Id | MGI:5921564 |
| Doi | 10.1038/ncomms16074 | Citation | Lin S, et al. (2017) Non-canonical NOTCH3 signalling limits tumour angiogenesis. Nat Commun 8:16074 |
| abstractText | Notch signalling is a causal determinant of cancer and efforts have been made to develop targeted therapies to inhibit the so-called canonical pathway. Here we describe an unexpected pro-apoptotic role of Notch3 in regulating tumour angiogenesis independently of the Notch canonical pathway. The Notch3 ligand Jagged-1 is upregulated in a fraction of human cancer and our data support the view that Jagged-1, produced by cancer cells, is inhibiting the apoptosis induced by the aberrant Notch3 expression in tumour vasculature. We thus present Notch3 as a dependence receptor inducing endothelial cell death while this pro-apoptotic activity is blocked by Jagged-1. Along this line, using Notch3 mutant mice, we demonstrate that tumour growth and angiogenesis are increased when Notch3 is silenced in the stroma. Consequently, we show that the well-documented anti-tumour effect mediated by gamma-secretase inhibition is at least in part dependent on the apoptosis triggered by Notch3 in endothelial cells. |
