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