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

• Published in: OncoTargets and therapy Vol. 11; pp. 7493 - 7501
• Main Authors: Zhou, Xiaoming, Yang, Fangfei, Zhang, Qin, Miao, Yuan, Hu, Xuejun, Li, Ailin, Hou, Gang, Wang, Qiuyue, Kang, Jian
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 2018; Taylor & Francis Ltd; Dove Medical Press
• Subjects: Adenocarcinoma; Apoptosis; Cancer metastasis; Cancer staging; Carcinoma; Cell adhesion & migration; Cell cycle; Chemotherapy; FAK; FAM129B; Gene expression; Hospitals; Immunoglobulins; Immunohistochemistry; invasion; Kinases; Lung cancer; Melanoma; Metastasis; Motility; Non-small cell lung cancer; Non-small cell lung carcinoma; Original Research; Patient outcomes; Plasmids; Prognosis; proliferation; Proteins; Radiation therapy; Small cell lung cancer; Surgery; Survival analysis; Tumors; United States > US; China; non-small cell lung cancer; FAK; invasion; proliferation; FAM129B
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S161852

Family with sequence similarity 129, member B ( ), also called MINERVA, is upregulated and promotes tumor invasion in multiple types of cancer. However, the mechanism and clinicopathological significance of remains unclear. Online KM-plotter tool and immunohistochemistry were used to predict the prognostic value of expression in lung cancer tissues. Western blotting analysis, MTT, colony formation assay and matrigel invasion assay were performed after overexpressing or depleting . In this study, using the online KM-plotter tool, we found was correlated with adverse outcome in non-small cell lung cancer (NSCLC) patients ( <0.001). Immunohistochemistry results revealed that 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 in clinical NSCLC tissue samples (77/187, 41.2%) was significantly higher than that in normal lung tissue samples (8/68, 11.8%; <0.001). expression associated with advanced TNM staging ( <0.001) and positive regional lymph node metastasis ( <0.001). The results of Kaplan-Meier analysis suggested that the survival time of patients with positive expression was significantly shorter than those with negatively expression ( <0.001). Proliferation and invasion assay revealed that prominently facilitated tumor proliferation and invasion in NSCLC cells. Western blotting results revealed that 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 overexpression. Our results indicated that 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.