FAM110B Inhibits Non-small Cell Lung Cancer Cell Proliferation And Invasion Through Inactivating Wnt/?-catenin Signaling

Purpose: FAM110 B is a member of the FAM110 family(family with sequence similarity 110),which is a component of the centrosome associated proteins.Previous studies have shown that FAM110 B may be involved in the process of cell cycle and may play a role in carcinogenesis and tumor progression.Using an online database,we found that FAM110 B may predict favorable prognosis in non-small cell lung cancer(NSCLC).Therefore,the role of FAM110 B playing in NSCLC needs to be further investigated.Patients and methods: Online databases and immunohistochemistry were used to predict the expression and prognostic value of FAM110 B in NSCLC samples.Immunofluorescence staining was used to investigate the subcellular distribution of FAM110 B.Western blot,MTT,colony formation,and matrigel invasion assay were used to detect the expression and the effect of FAM110 B on mediating proliferation and invasion in NSCLC cell lines.Results: In this study,immunohistochemistry results showed that FAM110 B expression significantly correlated with early TNM staging(P=0.020)and negative regional lymph node metastasis(P=0.006).Kaplan-Meier survival analysis found that the median survival time of patients with positive FAM110 B expression(56.181±2.348 months)was significantly longer than those with negative FAM110 B expression(47.701±2.997 months,P=0.024).Moreover,overexpression of FAM110 B inhibited the proliferation and invasion of A549,H1299 and LK2 cell lines.Conversely,FAM110 B RNAi exerted opposite effects in above cell lines.Furthermore,FAM110 B overexpression downregulated the active ??catenin,phosphorylation of GSK-3?(p-GSK-3?),cyclin B1,cyclin D1,MMP2 and MMP7,and upregulated the phosphorylation of ?-catenin(p-?-catenin)in A549 and H1299 cells.Besides,the FAM110 Binduced depression of p-GSK-3? and active ?-catenin were reversed after being treated with Wnt/?-catenin inhibitor,XAV-939.Conclusion: In summary,our results demonstrated that the overexpression of FAM110 B restricts the proliferation and invasion of NSCLC cells by inhibiting Wnt/?-catenin signaling.Our study reveals the antitumor function of FAM110 B in NSCLC and indicates that FAM110 B is a potential therapeutic target.