| First Author | Chen JY | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 5454 |
| PubMed ID | 28710382 | Mgi Jnum | J:252888 |
| Mgi Id | MGI:5927084 | Doi | 10.1038/s41598-017-05707-0 |
| Citation | Chen JY, et al. (2017) Netrin-1 promotes glioma growth by activating NF-kappaB via UNC5A. Sci Rep 7(1):5454 |
| abstractText | 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-kappaB p65ser536 phosphorylation and c-Myc expression in vitro and in vivo. Interestingly, activation of NF-kappaB by netrin-1 was dependent on UNC5A receptor, because suppression of UNC5A significantly inhibited NF-kappaB p65ser536 phosphorylation, c-Myc up-regulation and reduced cell proliferation. Taken together, these results suggested netrin-1 promotes glioma cell proliferation by activating NF-kappaB signaling via UNC5A, netrin-1 may be a potential therapeutic target for the treatment of glioma. |
