Research ArticleCancer

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

Sci. Signal.  07 Aug 2012:
Vol. 5, Issue 236, pp. ra57
DOI: 10.1126/scisignal.2002456

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Nucleolar Netrin

Ribosomes 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 ΔN-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 ΔN-netrin-1 increased the cytoplasmic pool of ribosomes, proliferation of cultured cells, and tumor growth in an in vivo model. ΔN-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 ΔN-netrin-1.