OncoTargets and Therapy (Oct 2018)
FAM129B promoted tumor invasion and proliferation via facilitating the phosphorylation of FAK signaling and associated with adverse clinical outcome of non-small cell lung cancer patients
Abstract
Xiaoming Zhou,1 Fangfei Yang,2 Qin Zhang,2 Yuan Miao,3 Xuejun Hu,4 Ailin Li,5 Gang Hou,2 Qiuyue Wang,2 Jian Kang2 1Department of Respiratory Medicine, The Shengjing Hospital of China Medical University, Shenyang, China; 2Department of Respiratory Medicine, The First Hospital of China Medical University, Shenyang, China; 3Department of Pathology, The First Hospital and College of Basic Medical Sciences, China Medical University, Shenyang, China; 4Department of Respiratory Disease in Geratology, The First Hospital of China Medical University, Shenyang, China; 5Department of Radiotherapy, The First Hospital of China Medical University, Shenyang, China Background: Family with sequence similarity 129, member B (FAM129B), also called MINERVA, is upregulated and promotes tumor invasion in multiple types of cancer. However, the mechanism and clinicopathological significance of FAM129B remains unclear. Materials and methods: Online KM-plotter tool and immunohistochemistry were used to predict the prognostic value of FAM129B expression in lung cancer tissues. Western blotting analysis, MTT, colony formation assay and matrigel invasion assay were performed after overexpressing or depleting FAM129B. Results: In this study, using the online KM-plotter tool, we found FAM129B was correlated with adverse outcome in non-small cell lung cancer (NSCLC) patients (P<0.001). Immunohistochemistry results revealed that FAM129B showed negative or dim expression in normal lung tissues while presented positive cytoplasmic expression in both squamous cell lung carcinoma and lung adenocarcinoma. The positive ratio of FAM129B in clinical NSCLC tissue samples (77/187, 41.2%) was significantly higher than that in normal lung tissue samples (8/68, 11.8%; P<0.001). FAM129B expression associated with advanced TNM staging (P<0.001) and positive regional lymph node metastasis (P<0.001). The results of Kaplan-Meier analysis suggested that the survival time of patients with positive FAM129B expression was significantly shorter than those with negatively FAM129B expression (P<0.001). Proliferation and invasion assay revealed that FAM129B prominently facilitated tumor proliferation and invasion in NSCLC cells. Western blotting results revealed that FAM129B upregulated the expression of MMP2 and Cyclin D1 by enhancing the phosphorylation of FAK at Tyr 397 and Tyr 925. Incorporation of FAK inhibitor in the medium significantly downregulated the phosphorylation of FAK and subsequently attenuated increasing expression of MMP2 and Cyclin D1 induced by FAM129B overexpression. Conclusion: Our results indicated that FAM129B may be a new prognosis predictor of NSCLC patients and impact tumor invasion and proliferation of NSCLC cells through promoting the activation of FAK signaling. Keywords: FAM129B, invasion, proliferation, FAK, non-small cell lung cancer
