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PDBsum entry 4ove
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References listed in PDB file
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Key reference
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Title
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Structural decoding of the netrin-1/unc5 interaction and its therapeutical implications in cancers.
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Authors
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M.Grandin,
M.Meier,
J.G.Delcros,
D.Nikodemus,
R.Reuten,
T.R.Patel,
D.Goldschneider,
G.Orriss,
N.Krahn,
A.Boussouar,
R.Abes,
Y.Dean,
D.Neves,
A.Bernet,
S.Depil,
F.Schneiders,
K.Poole,
R.Dante,
M.Koch,
P.Mehlen,
J.Stetefeld.
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Ref.
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Cancer Cell, 2016,
29,
173-185.
[DOI no: ]
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PubMed id
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Abstract
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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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