Ikappa B kinase alpha involvement in the development of nasopharyngeal carcinoma through a NF-κB-independent and ERK-dependent pathway

SummaryObjectivesIkappa B kinase alpha (IKKα) plays an inhibitory role in the development of epithelial-derived tumors. However, its specific function in the development of nasopharyngeal carcinoma (NPC) remains unknown. In this study we identify the role and mechanism of IKKα in IKKα-mediated NPC development.Material and methodsThe effect of IKKα on migration, invasion and tumorigenesis of NPC cell lines was determined using in vitro and in vivo studies. SUNE-1-5-8F cells transfected to overexpress IKKα, SUNE-1-6-10B cells with shRNA-mediated knockdown of IKKα, and three NPC cell lines were studied using Western blotting techniques to compare the major molecules in NF-κB pathways. Additionally, the extracellular signal-regulated kinase (ERK) pathway and matrix metalloproteinases (MMPs) in IKKα-regulated NPC and the effect of Epstein-Barr Nuclear Antigen 1 (EBNA1) on IKKα were examined.ResultsIKKα was underexpressed in highly invasive SUNE-1-5-8F cells compared with non-invasive cells (SUNE-1 and SUNE-6-10B). Overexpression of IKKα in SUNE-1-5-8F cells was achieved through transfection and resulted in inhibited migration and invasion in vitro. Furthermore, IKKα inhibited tumorigenesis in mice inoculated with IKKα-transfected NPC cells in vivo. These processes were independent of the conventional effect of IKKα on Nuclear factor κB (NF-κB) pathways. The ERK pathway was involved in IKKα-related NPC inhibition. Phosphorylation of ERK1/2 and subsequent secretion of MMP-9 were inhibited by the ERK inhibitor U0126 and not regulated by overexpressed IKKα. EBNA1 knockdown using small interfering RNA (siRNA) did not alter the expression of IKKα.ConclusionIncrease in IKKα expression suppresses the progression of NPC through a NF-κB-independent and ERK-dependent pathway.