RT Journal Article
SR Electronic
T1 Nucleolar Localization of a Netrin-1 Isoform Enhances Tumor Cell Proliferation
JF Science Signaling
JO Sci. Signal.
FD American Association for the Advancement of Science
SP ra57
OP ra57
DO 10.1126/scisignal.2002456
VO 5
IS 236
A1 Delloye-Bourgeois, Céline
A1 Goldschneider, David
A1 Paradisi, Andrea
A1 Therizols, Gabriel
A1 Belin, Stéphane
A1 Hacot, Sabine
A1 Rosa-Calatrava, Manuel
A1 Scoazec, Jean-Yves
A1 Diaz, Jean-Jacques
A1 Bernet, Agnès
A1 Mehlen, Patrick
YR 2012
UL http://stke.sciencemag.org/content/5/236/ra57.abstract
AB 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.