In:
Scientific Reports, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2017-07-14)
Kurzfassung:
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 path-finding, 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-κB p65 ser536 phosphorylation and c-Myc expression in vitro and in vivo . Interestingly, activation of NF-κB by netrin-1 was dependent on UNC5A receptor, because suppression of UNC5A significantly inhibited NF-κB p65 ser536 phosphorylation, c-Myc up-regulation and reduced cell proliferation. Taken together, these results suggested netrin-1 promotes glioma cell proliferation by activating NF-κB signaling via UNC5A, netrin-1 may be a potential therapeutic target for the treatment of glioma.
Materialart:
Online-Ressource
ISSN:
2045-2322
DOI:
10.1038/s41598-017-05707-0
Sprache:
Englisch
Verlag:
Springer Science and Business Media LLC
Publikationsdatum:
2017
ZDB Id:
2615211-3
