ADORA1 promotes nasopharyngeal carcinoma cell progression through regulation of PI3K/AKT/GSK-3β/β-catenin signaling

Abstract

AimsFor most human cancers, the expression pattern and biological function of ADORA1 (Adenosine A1 Receptor) are largely unknown. This study has been designed to explore the clinical significance and the mechanism of ADORA1 in nasopharyngeal carcinoma (NPC) cells. Materials and methodsThe level of ADORA1 in NPC and its adjacent tissues was analyzed by IHC, real-time PCR and western blotting. MTT and colony formation assays were used to determine the cell viability post ADORA1 overexpression or knockdown. Wound-healing assay and Transwell assay were used to analyze the effect of ADORA1 on migration and invasion. Moreover, the effect of ADORA1 on tumor growth was also studied in vivo by using xenograft mouse model. The regulation of ADORA1 on PI3K/AKT/GSK-3β/β-catenin pathway was determined by western blotting and TOP-Flash luciferase assay. Key findingsPrimary NPC exhibits overexpression of ADORA1, which is related to the overexpression of its mRNA. Ectopic expression of ADORA1 promotes the proliferation, invasion and migration in NPC cells. The apoptosis, however, is suppressed. ADORA1 silencing was found to exert opposite effects in in vitro studies and produced a significant inhibitory effect on murine xenograft tumor growth in vivo experiments. Besides, ADORA1 also triggers the PI3K/AKT/GSK-3β/β-catenin intracellular oncogenic pathway for signal transduction. Inhibition of this pathway by PI3K inhibitor LY294002 obstructed the impact of ADORA1 on tumor development in cells with ADORA1-overexpression. SignificanceADORA1 has been identified as an important oncoprotein, promoting tumor cell proliferation via PI3K/AKT/GSK-3β/β-catenin signaling pathway in NPC.