| First Author | Larrieu-Lahargue F | Year | 2011 |
| Journal | Circ Res | Volume | 109 |
| Issue | 7 | Pages | 770-4 |
| PubMed ID | 21799154 | Mgi Jnum | J:188830 |
| Mgi Id | MGI:5442275 | Doi | 10.1161/CIRCRESAHA.111.247239 |
| Citation | Larrieu-Lahargue F, et al. (2011) Netrin-4 activates endothelial integrin {alpha}6{beta}1. Circ Res 109(7):770-4 |
| abstractText | RATIONALE: Netrin-4 regulates vascular development. Identity of netrin-4 endothelial receptor and its subsequent cell functions is controversial. We previously demonstrated that the inhibition of netrin-1 canonical receptors, Unc5B and neogenin, expressed by lymphatic endothelial cells, do not suppress netrin-4-induced cell signaling and functions. Netrin family members were shown to signal through a range of receptors, including integrins (such as alpha3beta1, alpha6beta1, and alpha6beta4) in nonendothelial cells. OBJECTIVE: We tested whether integrins are netrin-4 receptors in the endothelium. METHODS AND RESULTS: The alpha6beta1 integrin is expressed by endothelial cells, and binds netrin-4 in a dose-dependent manner. Inhibition of alpha6 or beta1 integrin subunits suppresses netrin-4-induced endothelial cell migration, adhesion, and focal adhesion contact. Netrin-4-stimulated phosphorylation of Src kinase family, effectors of endothelial cell migration, is also abolished by alpha6 or beta1 inhibition. Finally, netrin-4 and alpha6beta1 integrin expression colocalize in mouse embryonic, intestine, and tumor vasculature. CONCLUSIONS: The alpha6beta1 integrin is a netrin-4 receptor in lymphatic endothelium and consequently represents a potential target to inhibit netrin-4-induced metastatic dissemination. |
