G-protein-coupled receptor kinase-5 promotes glioblastoma progression by targeting the nuclear factor kappa B pathway

American Journal of Translational Research

Chuan-Dong Cheng¹  Jing-Jing Wu²  Yong-Fei Dong³  De-Jun Bao⁴  Yang Yang⁵ 

[1] Anhui Province Key Laboratory of Brain Function and Brain Disease, Hefei 230001, Anhui Province, P. R. China;Department of Neurosurgery, The First Affiliated Hospital of University of Science and Technology of China, Hefei 230001, Anhui Province, P. R. China;Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, Hefei 230601, Anhui Province, P. R. China;Institute of Clinical Pharmacology of Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-Inflammatory and Immune Medicine, Hefei 230032, Anhui Province, P. R. China;Shandong University, Jinan, Shandong Province, P. R. China

关键词: Glioma;    G-protein-coupled receptor kinase-5;    nuclear factor kappa B;    proliferation;    glioma stem cell;    blood vessel;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

G-protein-coupled receptor kinase-5 (GRK5) plays essential roles in multiple celluar events. However, its role in the development and progression of glioma is poorly understood. In this research, we found that GRK5 is significantly upregulated in human gliomas. For the first time, a close relationship was noted between GRK5 expression and blood vessel development in human glioma. Specifically co-expression of GRK5 and the tumor stem cell marker CD133 was observed in the cytoplasm of high grade glioma cells. The depletion of GRK5 suppressed the proliferation, migration and invasion in glioma cells, and promoted apoptosis. We next discovered that GRK5 knockdown inhibits the nuclear factor kappa B (NF-κB) pathway, thus resulting in downregulation of key downstream secretory products CCL2, IL-6 and IL-8 in glioma cell conditioned medium (CM). In addition, treatment of cells with the NF-κB stimulator PMA reversed this effect and increased the GRK5 level. Our results demonstrate an oncogenic role for GRK5 and reveal an activation of the GRK5-NF-κB pathway during the malignant progression of glioma.

【 授权许可】

CC BY-NC