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.