Identification Of A Metastasis-related Protein IFI16 In Esophageal Cancer Using A Proteomic Approach

Metastasis is the leading cause of the high morality of esophageal squamous cell carcinoma(ESCC),so early monitoring metastasis of esophageal cancer is the key to improve the survival rate of ESCC patients.However,there have not been effective biomarkers for predicting metastasis of ESCC patients,it is an urgent need to identify ESCC metastasis-related proteins.Here,the proteomic characterization analysis was performed in highly metastatic 30 M cell established in our previous study and the corresponding parental cells KYSE30.The data showed that IFI16 was upregulated in30 M cell with high metastasis capability compared with parental KYSE30 cell.IFI16 also increased in ESCC tumor compared with non-tumor issue.Kaplan-Meier survival curve analysis showed that the relapse-free survival(RFS)of patients with high IFI16 level was worse than that of patients with low IFI16 level(P=0.0449).In addition,IFI16 knockdown did not affect the cell growth,but inhibited ESCC cell migration and invasion in ESCC cells.Moreover,IFI16 knockdown suppressed the lung metastasis of 30 M cells in mouse models.Finally,to clarify the mechanism of IFI16 promoting ESCC cell metastasis,we performed an RNA-Seq assay in IFI16-knocking down 30 M cells and identified that knocking down IFI16 downregulated the expression of fibroblast growth factor proteins(FGF1,FGF2 etc).Furthermore,overexpressing FGF1 rescued the lost of migration and invasion ability of 30 M mediated by IFI16 knockdown.Collectively,our results demonstrated that IFI16 was a key ESCC metastasis-related protein and played a role in ESCC metastasis through promoting the FGF proteins expression.