OncoTargets and Therapy (May 2020)
FAM110B Inhibits Non-Small Cell Lung Cancer Cell Proliferation and Invasion Through Inactivating Wnt/β-Catenin Signaling
Abstract
Menghua Xie,1 Lin Cai,1 Jingduo Li,1 Jing Zhao,1 Yingxue Guo,1 Zaiyu Hou,1 Xiupeng Zhang,1 Hua Tian,2 Ailin Li,2 Yuan Miao1 1Department of Pathology, The College of Basic Medical Sciences and The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China; 2Department of Radiotherapy, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: Yuan Miao Tel +86 248 328 2248Email [email protected]: FAM110B 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 FAM110B 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 FAM110B may predict favorable prognosis in non-small cell lung cancer (NSCLC). Therefore, the role of FAM110B 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 FAM110B in NSCLC samples. Immunofluorescence staining was used to investigate the subcellular distribution of FAM110B. Western blot, MTT, colony formation, and matrigel invasion assay were used to detect the expression and the effect of FAM110B on mediating proliferation and invasion in NSCLC cell lines.Results: In this study, immunohistochemistry results showed that FAM110B 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 FAM110B expression (56.181± 2.348 months) was significantly longer than those with negative FAM110B expression (47.701± 2.997 months, P=0.024). Moreover, overexpression of FAM110B inhibited the proliferation and invasion of A549, H1299, and LK2 cell lines. Conversely, FAM110B RNAi exerted opposite effects in the above cell lines. Furthermore, FAM110B overexpression downregulated the active β‐catenin, phosphorylation of GSK-3β (p-GSK-3β), cyclin B1, cyclin D1, MMP2, and MMP7, and upregulated the phosphorylation of β-catenin (p-β-catenin) in A549 and H1299 cells. Besides, the FAM110B-induced depressions of p-GSK-3β and active β-catenin were reversed after being treated with Wnt/β-catenin inhibitor, XAV-939.Conclusion: In summary, our results demonstrated that the overexpression of FAM110B restricts the proliferation and invasion of NSCLC cells by inhibiting Wnt/β-catenin signaling. Our study reveals the antitumor function of FAM110B in NSCLC and indicates that FAM110B is a potential therapeutic target.Keywords: FAM110B, NSCLC, Wnt/β-catenin signaling, proliferation, invasion
