KISS1 gene suppresses metastasis of nasopharyngeal cancer via activation of the ERK1/2 pathway

Abstract

Nasopharyngeal cancer (NPC) is one of the most common head and neck cancers in the world. The failure of the treatment of NPC is mainly caused by the metastasis of the cancer cells. There is a great need to study the mechanism of metastasis for accurate diagnosis, prognosis and efficient therapeutic strategy. The KISS1 gene has already been reported as a metastasis suppressor in numerous cancers. In this study, by integrating the Transwell assay, western blotting and real-time reverse transcriptase polymerase chain reaction (RT-PCR) analysis, we found that the expression of KISS1 and its receptor gene (hOT7T175, KISS1R) negatively related with the metastasis of NPC cells. Overexpression of the KISS1 and KISS1R genes reduced migration and invasion of the SUNE-1-5-8F cells that are a cell line of NPC. Additionally, overexpression of these genes significantly increased the phosphorylation of focal adhesion kinase (FAK) and decreased the expression of ezrin (EZR), indicated by western blotting. Further study showed the metastasis suppression role of KISS1 and KISS1R was mediated though phosphorylation of the ERK1/2 pathway for that blocking the phosphorylation of the pathway with inhibitor (PD98059) reversed the metastasis suppression and phosphorylation of FAK as well as up-regulation of EZR simultaneously. Together, all of these results suggested for the first time that KISS1 and KISS1R suppress the metastasis of NPC cells by phosphorylation of FAK and decreasing EZR through phosphorylation of the ERK1/2 pathway.