Abstract:
:Netrin-1 displays proto-oncogenic activity in several cancers, which is thought to be due to the ability of this secreted cue to stimulate survival when bound to its receptors. We showed that in contrast to full-length, secreted netrin-1, some cancer cells produced a truncated intranuclear form of netrin-1 (ΔN-netrin-1) through an alternative internal promoter. Because of a nucleolar localization signal located in its carboxyl terminus, ΔN-netrin-1 was targeted to the nucleolus, where it interacted with nucleolar proteins, affected nucleolar ultrastructure, and interacted with the promoters of ribosomal genes. Moreover, ΔN-netrin-1 stimulated cell proliferation in vitro and tumor growth in vivo. Thus, some cancer cells produce not only a full-length, secreted form of netrin-1 that promotes cell survival but also a truncated netrin-1 that stimulates cell proliferation, potentially by enhancing ribosome biogenesis.
journal_name
Sci Signaljournal_title
Science signalingauthors
Delloye-Bourgeois C,Goldschneider D,Paradisi A,Therizols G,Belin S,Hacot S,Rosa-Calatrava M,Scoazec JY,Diaz JJ,Bernet A,Mehlen Pdoi
10.1126/scisignal.2002456subject
Has Abstractpub_date
2012-08-07 00:00:00pages
ra57issue
236eissn
1945-0877issn
1937-9145pii
5/236/ra57journal_volume
5pub_type
杂志文章abstract::New therapeutic approaches for chronic inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis, and psoriasis are needed because current treatments are often suboptimal in terms of both efficacy and the risks of serious adverse events. Inhibitor of apoptosis proteins (IAPs) are E3 ubiquitin liga...
journal_title:Science signaling
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journal_title:Science signaling
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journal_title:Science signaling
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journal_title:Science signaling
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journal_title:Science signaling
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journal_title:Science signaling
pub_type: 社论
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journal_title:Science signaling
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