Sci. Signal., 7 August 2012
Nucleolar NetrinRibosomes are the cellular sites for protein synthesis, and ribosomal RNA is transcribed in nuclear structures called nucleoli. The higher proliferation rate of tumor cells requires an increased rate of protein synthesis, and enhancing the rates of ribosomal RNA transcription and the production of ribosomes confers a growth advantage. Delloye-Bourgeois et al. characterized a truncated isoform of netrin-1 called N-netrin-1 that, unlike the full-length form, was not secreted but instead localized to nucleoli where it interacted with proteins involved in ribosomal RNA transcription. Overexpression of N-netrin-1 increased the cytoplasmic pool of ribosomes, proliferation of cultured cells, and tumor growth in an in vivo model. N-netrin-1 was also detected in some cancer cell lines and human cancers. The current antitumor agents targeting the full-length netrin-1 isoform cannot enter cells and, thus, would likely not affect the pro-tumor activity of nucleolar N-netrin-1.
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).
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