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Publication : Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers.

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.
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