First Author | Grandin M | Year | 2016 |
Journal | Cancer Cell | Volume | 29 |
Issue | 2 | Pages | 173-85 |
PubMed ID | 26859457 | Mgi Jnum | J:231451 |
Mgi Id | MGI:5771592 | Doi | 10.1016/j.ccell.2016.01.001 |
Citation | Grandin M, et al. (2016) Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers. Cancer Cell 29(2):173-85 |
abstractText | Netrin-1 has been shown to be up-regulated in a fraction of human cancers as a mechanism to allow these tumors to escape the pro-apoptotic activity of some of its main dependence receptors, the UNC5 homologs (UNC5H). Here we identify the V-2 domain of netrin-1 to be important for its interaction with the Ig1/Ig2 domains of UNC5H2. We generate a humanized anti-netrin-1 antibody that disrupts the interaction between netrin-1 and UNC5H2 and triggers death of netrin-1-expressing tumor cells in vitro. We also present evidence that combining the anti-netrin-1 antibody with epidrugs such as decitabine could be effective in treating tumors showing no or modest netrin-1 expression. These results support that this antibody is a promising drug candidate. |