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

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

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29 Citas (Scopus)

Resumen

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.

Idioma originalEnglish
Número de artículo5454
PublicaciónScientific Reports
Volumen7
N.º1
DOI
EstadoPublished - dic. 1 2017

Nota bibliográfica

Funding Information:
We would like to thank Dr. Michael Klagsbrun (Boston Children's Hospital, Harvard Medical School, Boston) for providing the Netrin-1-V5-His plasmid containing the full-length netrin-1 cDNA and Deliang Cao (Southern Illinois University School of Medicine) for providing the construct of p65. This work was supported by the Program of International S and T Cooperation (2015DFA31580), the National Natural Science Foundation of China (31671065, 31401192), the Program for Introducing Talents to Universities (B07017), the Jilin Provincial Key Laboratory of Neural Plasticity (20160622020JC), the Fundamental Research Funds for the Central Universities of China (2412016KJ042), and the Science and Technology Development Plan of Jilin Province (20140520030JH, 20140203002YY, 20150520031JH). D.X.L.'s research program is supported by the New Zealand Breast Cancer Foundation, the Breast Cancer Cure charities, the Auckland Medical Research Foundation and the Health Research Council of New Zealand.

Publisher Copyright:
© 2017 The Author(s).

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