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

Abstract 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 sever...

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Autores principales:	Jing-Ying Chen, Xiao-Xiao He, Chi Ma, Xin-Min Wu, Xi-Lin Wan, Zhen-Kai Xing, Qing-Qing Pei, Xian-Ping Dong, Dong-Xu Liu, Wen-Cheng Xiong, Xiao-Juan Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/015c1e8f4b734688ae400d727538ff50
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spelling	oai:doaj.org-article:015c1e8f4b734688ae400d727538ff502021-12-02T12:30:46ZNetrin-1 promotes glioma growth by activating NF-κB via UNC5A10.1038/s41598-017-05707-02045-2322https://doaj.org/article/015c1e8f4b734688ae400d727538ff502017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05707-0https://doaj.org/toc/2045-2322Abstract 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 p65ser536 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 p65ser536 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.Jing-Ying ChenXiao-Xiao HeChi MaXin-Min WuXi-Lin WanZhen-Kai XingQing-Qing PeiXian-Ping DongDong-Xu LiuWen-Cheng XiongXiao-Juan ZhuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing-Ying Chen Xiao-Xiao He Chi Ma Xin-Min Wu Xi-Lin Wan Zhen-Kai Xing Qing-Qing Pei Xian-Ping Dong Dong-Xu Liu Wen-Cheng Xiong Xiao-Juan Zhu Netrin-1 promotes glioma growth by activating NF-κB via UNC5A
description	Abstract 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 p65ser536 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 p65ser536 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.
format	article
author	Jing-Ying Chen Xiao-Xiao He Chi Ma Xin-Min Wu Xi-Lin Wan Zhen-Kai Xing Qing-Qing Pei Xian-Ping Dong Dong-Xu Liu Wen-Cheng Xiong Xiao-Juan Zhu
author_facet	Jing-Ying Chen Xiao-Xiao He Chi Ma Xin-Min Wu Xi-Lin Wan Zhen-Kai Xing Qing-Qing Pei Xian-Ping Dong Dong-Xu Liu Wen-Cheng Xiong Xiao-Juan Zhu
author_sort	Jing-Ying Chen
title	Netrin-1 promotes glioma growth by activating NF-κB via UNC5A
title_short	Netrin-1 promotes glioma growth by activating NF-κB via UNC5A
title_full	Netrin-1 promotes glioma growth by activating NF-κB via UNC5A
title_fullStr	Netrin-1 promotes glioma growth by activating NF-κB via UNC5A
title_full_unstemmed	Netrin-1 promotes glioma growth by activating NF-κB via UNC5A
title_sort	netrin-1 promotes glioma growth by activating nf-κb via unc5a
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/015c1e8f4b734688ae400d727538ff50
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Netrin-1 promotes glioma growth by activating NF-κB via UNC5A

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