Netrin-1 promotes glioma growth by activating NF-κB via UNC5A

Gliomas, a common type of brain tumor, are characterized by aggressive infiltration, making it difficultly to cure by surgery. Netrin-1, an extracellular guidance cue critical for neuronal axon pathfinding, has been reported to play an important role in cell invasion and migration in several types of cancers. However, the role of netrin-1 in glioma remains largely unknown. Here, we provide evidence suggested that Netrin-1 has a critical role in glioma growth. We found that netrin-1 was significantly increased in glioma samples and positively correlated with cell proliferation, tumor grade and malignancy. Netrin-1 knockdown reduced cell proliferation and attenuated tumor growth in a xenograft mouse model. Further studies found that netrin-1 induced NF-kappa B p65(ser536) phosphorylation and c-Myc expression in vitro and in vivo. Interestingly, activation of NF-kappa B by netrin-1 was dependent on UNC5A receptor, because suppression of UNC5A significantly inhibited NF-kappa B p65ser536 phosphorylation, c-Myc up-regulation and reduced cell proliferation. Taken together, these results suggested netrin-1 promotes glioma cell proliferation by activating NF-kappa B signaling via UNC5A, netrin-1 may be a potential therapeutic target for the treatment of glioma.