Upregulation of Family with Sequence Similarity 83 Member D Expression Enhances Cell Proliferation and Motility Via Activation of Wnt/β-catenin Signaling and Predicts Poor Prognosis in Gastric Cancer

BACKGROUND/AIMS:Gastric cancer (GC) is the third most common cause of cancer-related death worldwide. The molecular mechanisms underlying the progression of gastric cancer are still not fully elucidated. In this study, we focused on exploring the role of family with sequence similarity 83, member D (FAM83D) in gastric cancer progression.METHODS:The expression of FAM83D in GC tissues was detected by immunohistochemistry (IHC) staining. FAM83D knockdown or overexpression were constructed in AGS and SGC-7901 cells with two distinct siRNA duplexes and lentivirus infection, respectively, to explore the role of FAM83D in gastric cancer progression. Nude mouse xenograft assay was used to further explore the role of FAM83D in tumorigenesis in vivo.RESULTS:We found that FAM83D mRNA and protein levels were higher in human GC tumor tissues and in GC cell lines, compared with the adjacent normal tissues and non-malignant gastric epithelial cell lines, respectively, and that higher FAM83D expression was correlated with worse overall survival (p<0.0001) and disease-free survival (p<0.0001) in GC patients. Additionally, our results showed that FAM83D overexpression significantly enhanced the proliferation, clonogenicity, and motility of GC cells, whereas FAM83D depletion caused a dramatic increase in the number of cells arrested at the G1 phase of the cell cycle. Consistent with these findings from in vitro experiment, our data also indicated that FAM83D knockdown significantly repressed GC tumor growth in vivo. Furthermore, we demonstrated that FAM83D depletion was associated with reduced Wnt/β-catenin signaling.CONCLUSIONS:This study suggested that FAM83D overexpression enhanced the proliferation, clonogenicity, and motility of GC cells by activating Wnt/β-catenin signaling, and FAM83D may be a promising diagnostic and therapeutic target for human GC.