Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. Signal., 7 August 2012
Vol. 5, Issue 236, p. ra57
[DOI: 10.1126/scisignal.2002456]

RESEARCH ARTICLES

Nucleolar Localization of a Netrin-1 Isoform Enhances Tumor Cell Proliferation

Céline Delloye-Bourgeois1*, David Goldschneider1*, Andrea Paradisi1*, Gabriel Therizols2*, Stéphane Belin2, Sabine Hacot2, Manuel Rosa-Calatrava3, Jean-Yves Scoazec4, Jean-Jacques Diaz2{dagger}, Agnès Bernet1{dagger}, and Patrick Mehlen1{dagger}{ddagger}

1 Apoptosis, Cancer and Development Laboratory–Equipe labellisée "La Ligue," LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052–CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
2 Nuclear Domains and Pathologies team, Centre de Cancérologie de Lyon, INSERM U1052–CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.
3 CNRS-UCBL FRE3011, Laboratoire de Virologie et Pathologie Humaine, Faculté Laennec, 69372 Lyon cedex 08, France.
4 Endocrine Differentiation Laboratory, Centre de Cancérologie de Lyon, INSERM U1052–CNRS UMR5286, Université de Lyon, Hospices Civils de Lyon, Hôpital Edouard Herriot, Anatomie Pathologique, 69437 Lyon, France.

* These authors contributed equally to this work.

{dagger} Senior authors.

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 ({Delta}N-netrin-1) through an alternative internal promoter. Because of a nucleolar localization signal located in its carboxyl terminus, {Delta}N-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, {Delta}N-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.

{ddagger} To whom correspondence should be addressed. E-mail: patrick.mehlen{at}lyon.unicancer.fr

Citation: C. Delloye-Bourgeois, D. Goldschneider, A. Paradisi, G. Therizols, S. Belin, S. Hacot, M. Rosa-Calatrava, J.-Y. Scoazec, J.-J. Diaz, A. Bernet, P. Mehlen, Nucleolar Localization of a Netrin-1 Isoform Enhances Tumor Cell Proliferation. Sci. Signal. 5, ra57 (2012).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Revisiting the Nucleolus: From Marker to Dynamic Integrator of Cancer Signaling.
D. Ruggero (2012)
Science Signaling 5, pe38
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882