Abstract

Glioblastomas (GBMs) are the most prevalent and devastating primary intracranial malignancies and have extensive heterogeneity. Notch1 signaling is a more complex process in the development of numerous cell and tissue types, including gliomagenesis and progression, and is upregulated in glioma-initiating cells. However, the contradictory expression of Notch1 among lower grade gliomas and GBMs confounds our understanding of GBM biology and has made identifying effective therapies difficult. In this study, we validated that Notch1 and NF-κB(p65) are highly expressed in the classical and proneural subtypes of GBM using the data set from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). DAPT and shRNA targeting Notch1 decreased NF-κB(p65) expression, suppressed cell proliferation, and induced apoptosis of GBM cells in vitro and in vivo. Furthermore, we illustrated that the intracellular Notch could bind with NF-κB(p65) in GBM cells. These findings suggest that the cross-talk between Notch1 signaling and NF-κB(p65) could contribute to the proliferation and apoptosis of glioma, and this discovery could help drive the design of more effective therapies in Notch1-targeted clinical trials.

Details

Title
Notch1 is a prognostic factor that is distinctly activated in the classical and proneural subtype of glioblastoma and that promotes glioma cell survival via the NF-κB(p65) pathway
Author
Long, Hai 1 ; Zhang, Chen 2 ; Li, Tao 1 ; Zhou, Xingchen 3 ; Liu, Bo 3 ; Li, Shuai 3 ; Zhu, Meng 4 ; Lin, Yu 3 ; Yu, Shengping 3 ; Zhang, Kai 3 ; Ren, Bingcheng 3 ; Haolang Ming 3 ; Huang, Yubao 3 ; Chen, Lei 3 ; Zhao, Pengfei 3 ; Zhou, Hua 3 ; Jiang, Tao 5 ; Yang, Xuejun 6 

 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China; Key Laboratory of Post-Trauma Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education, Tianjin, China; Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin, China; Chinese Glioma Cooperative Group (CGCG), Beijing, China 
 Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA 
 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China; Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin, China 
 Department of Neurosurgery, The Affliated Hospital of Qingdao University, Qingdao, Shandong, China 
 Chinese Glioma Cooperative Group (CGCG), Beijing, China; Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China 
 Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China 
Pages
1-13
Publication year
2018
Publication date
Feb 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2019486352
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.