Grandin, Melodie, Meier, Markus ORCID: 0000-0003-1068-746X, Delcros, Jean Guy, Nikodemus, Denise ORCID: 0000-0003-4492-817X, Reuten, Raphael ORCID: 0000-0002-9434-4108, Patel, Trushar R. ORCID: 0000-0003-0627-2923, Goldschneider, David, Orriss, George, Krahn, Natalie, Boussouar, Amina, Abes, Riad, Dean, Yann, Neves, David, Bernet, Agnes, Depil, Stephane, Schneiders, Fiona, Poole, Kate ORCID: 0000-0003-0879-6093, Dante, Robert, Koch, Manuel, Mehlen, Patrick and Stetefeld, Joerg ORCID: 0000-0003-1478-3248 (2016). Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers. Cancer Cell, 29 (2). S. 173 - 186. CAMBRIDGE: CELL PRESS. ISSN 1878-3686

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Grandin, MelodieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meier, MarkusUNSPECIFIEDorcid.org/0000-0003-1068-746XUNSPECIFIED
Delcros, Jean GuyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nikodemus, DeniseUNSPECIFIEDorcid.org/0000-0003-4492-817XUNSPECIFIED
Reuten, RaphaelUNSPECIFIEDorcid.org/0000-0002-9434-4108UNSPECIFIED
Patel, Trushar R.UNSPECIFIEDorcid.org/0000-0003-0627-2923UNSPECIFIED
Goldschneider, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Orriss, GeorgeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krahn, NatalieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boussouar, AminaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abes, RiadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dean, YannUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neves, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bernet, AgnesUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Depil, StephaneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneiders, FionaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poole, KateUNSPECIFIEDorcid.org/0000-0003-0879-6093UNSPECIFIED
Dante, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, ManuelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mehlen, PatrickUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Stetefeld, JoergUNSPECIFIEDorcid.org/0000-0003-1478-3248UNSPECIFIED
URN: urn:nbn:de:hbz:38-284712
DOI: 10.1016/j.ccell.2016.01.001
Journal or Publication Title: Cancer Cell
Volume: 29
Number: 2
Page Range: S. 173 - 186
Date: 2016
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 1878-3686
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GUIDANCE CUE NETRIN-1; CRYSTAL-STRUCTURE; AXON GUIDANCE; SURVIVAL FACTOR; BINDING; RECEPTORS; APOPTOSIS; COMPLEX; LAMININ; CHAINMultiple languages
Oncology; Cell BiologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/28471

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