Abstract: Objective:To explore the molecular mechanism of KISS1 and its receptor gene KISS1-R in adjusting the migration and invasion of nasopharyngeal carcinoma(NPC) cells via activating the ERK1/2 pathway.Methods:The expression levels of KISS1,KISS1-R and FAK were detected using RT-PCR and Western blot,the phosphorylation activation of ERK1/2 signaling pathway was identified,and the relationship between the expression of EZR protein,and migration and invasion of NPC cells was analyzed.The overexpression vector containing KISS1 and KISS1-R gene was constructed,the effects of overexpressing KISS1 and KISS1-R gene on the migration of SUNE-1-5-8F cells were detected using the wound healing assay and Transwell assay.After KISS1 and KISS1-R gene expressing,the levels of FAK,p-FAK,p-ERK1/2 and EZR protein were measured by Western blot.After the phosphorylation activation of ERK1/2 pathway was blocked,the effects of KISS1 and KISS1-R gene on the migration and invasion of NPC cells,and expression levels of p-FAK and EZR protein were identified.The expression of KISS1 was interfered with siRNA,and the effects of KISS1 gene on migration and invasion of NPC cells were assayed.Results:The results of RT-PCR showed that the expression of KISS1 gene was high in SUNE-1-6-10B cells compared with SUNE-1-5-8F cells.The results of Western blot showed that the expression levels of KISS1,KISS1-R,FAK and p-FAK were negatively related to metastasis of NPC cells,and the expression of EZR was positively correlated with the metastasis of NPC cells.The wound healing and Transwell assay showed that the overexpression of KISS1 and KISS1-R could effectively inhibit the migration and invasion of SUNE-1-5-8F cells.The results of Western blot showed that the overexpression of KISS1 and KISS1-R could improve the protein expression of p-FAK and p-ERK1/2,and inhibit the level of EZR expression.The migration and invasion suppression induced by overexpression of KISS1 and KISS1-R was reversed after the inhibitor PD98059 of ERK1/2 pathway was used.The overexpression of KISS1 and KISS1-R could lead to the recovery of the p-FAK and p-ERK1/2 upregulating and EZR downregulating.Inhibiting the KISS1 gene expression caused by siRNA interference could increase the migration and invasion of SUNE-1-5-8F cells.Conclusions:The KISS1 gene overexpression can significantly inhibit the migration and invasion of NPC cells.Inhibiting the KISS1 gene expression caused by siRNA interference can increase the migration and invasion of NPC cells.The KISS1 and KISS1-R gene can activate the ERK1/2 pathway,p-FAK,and inhibit the EZR expression through phosphorylation,which can inhibit the migration and invasion of NPC cells.