Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Grandin, Melodie UNSPECIFIED UNSPECIFIED UNSPECIFIED Meier, Markus UNSPECIFIED orcid.org/0000-0003-1068-746X UNSPECIFIED Delcros, Jean Guy UNSPECIFIED UNSPECIFIED UNSPECIFIED Nikodemus, Denise UNSPECIFIED orcid.org/0000-0003-4492-817X UNSPECIFIED Reuten, Raphael UNSPECIFIED orcid.org/0000-0002-9434-4108 UNSPECIFIED Patel, Trushar R. UNSPECIFIED orcid.org/0000-0003-0627-2923 UNSPECIFIED Goldschneider, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Orriss, George UNSPECIFIED UNSPECIFIED UNSPECIFIED Krahn, Natalie UNSPECIFIED UNSPECIFIED UNSPECIFIED Boussouar, Amina UNSPECIFIED UNSPECIFIED UNSPECIFIED Abes, Riad UNSPECIFIED UNSPECIFIED UNSPECIFIED Dean, Yann UNSPECIFIED UNSPECIFIED UNSPECIFIED Neves, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Bernet, Agnes UNSPECIFIED UNSPECIFIED UNSPECIFIED Depil, Stephane UNSPECIFIED UNSPECIFIED UNSPECIFIED Schneiders, Fiona UNSPECIFIED UNSPECIFIED UNSPECIFIED Poole, Kate UNSPECIFIED orcid.org/0000-0003-0879-6093 UNSPECIFIED Dante, Robert UNSPECIFIED UNSPECIFIED UNSPECIFIED Koch, Manuel UNSPECIFIED UNSPECIFIED UNSPECIFIED Mehlen, Patrick UNSPECIFIED UNSPECIFIED UNSPECIFIED Stetefeld, Joerg UNSPECIFIED orcid.org/0000-0003-1478-3248 UNSPECIFIED
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:	Keywords Language GUIDANCE CUE NETRIN-1; CRYSTAL-STRUCTURE; AXON GUIDANCE; SURVIVAL FACTOR; BINDING; RECEPTORS; APOPTOSIS; COMPLEX; LAMININ; CHAIN Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28471