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