MOB2 Suppresses Glioma Cell Migration And Invasion Through FAK/AKT Signaling Pathway

BackgroundGliomas comprise about 40 to 50 percent of all brain tumors and are the mostly found malignant tumors in brain.Glioma can be classified into 4 levels based on the WHO classification ranging from I to IV.Grade IV gliomas are also called glioblastoma multiform which remain the most devastating tumor.The exact cause of glioma is not well known.Invading into neighboring tissues and infiltrating growth are the primary characteristics of glioma which denote that traditional surgical operations and radiotherapy have limited effects.Thus the glioma patients have unfavorable prognosis.MOB family proteins are important components in Hippo signaling pathway.It was uncovered by researchers that MOB family proteins control cell proliferation,cell differentiation and apoptosis.MOB family proteins content six different proteins which are MOB1 A,MOB1B,MOB2,MOB3 A,MOB3B and MOB3 C.MOB2 was found to be able to interact with NDR1/2 and to regulate cell apoptosis and centrosome duplication.It was found by researchers that the expression level of MOB2 protein was prominently lower in hepatocellular carcinoma than in cancer-adjacent liver tissues.The expression level of MOB2 m RNA was found to be lower in patients with non small cell cancer compared to normal person.However there is no reports regarding the role of MOB2 in glioma.Cancer cell migration,invasion and metastasis are complex processes which involve multiple signaling pathways.FAK/AKT signaling pathway plays a major role in these processes.It was denoted by some researches that activated FAK can phosphorylate AKT which in turn activates downstream signaling pathway to enhance the migratory and invasive ability of cancer cell.ObjectiveOur research is to determine the expression profile and role of MOB2 in gliomas,along with its correlation with patients’ survival rate,thereby unveiling the molecular mechanism of MOB2 and providing a potential therapeutic insight for glioma treatment.Methods(1)Bioinformatics methods(NLP analysis,Gene ontology analysis,gene network and pathway analysis)were used to analyze data extracting from TCGA database to find the correlation between MOB2 expression and patients’ survival rate.(2)Immunohistochemistry staining was performed to investigate the positive rate of MOB2 protein in normal brain tissues and different grade glioma tissues.(3)Lentivirus-mediated overexpression and knockdown of MOB2 protein in glioma cell lines were used to test the influence of MOB2 on cell phenotype.(4)Western blot,immunofluorescence and small molecule inhibitors were used to investigate possible singling pathways that MOB2 participates in.Results(1)Big data analytics shows that MOB2 acts as a tumor suppressor in glioma.Its expression level positively correlated with patient’s survival rate and the expression of MOB2 was higher in normal brain tissues than that in glioma tissues.(2)Immunohistochemistry result shows that MOB2 had a higher positive rate in normal brain tissues than in glioma tissues.(3)Transwell migration and invasion assays uncover that knockdown of MOB2 enhanced the ability of cell migration and invasion of glioma cell lines while overexpression of MOB2 had the opposite effect.(4)Immunofluorescence analysis shows that knockdown of MOB2 upregulated the number of focal adhesions while overexpression of MOB2 reduced the number of focal adhesions.(5)Western blot and small molecule inhibitor assays indicate that MOB2 regulated cell migration and invasion through FAK/AKT signaling pathway.Conclusions(1)MOB2 is a tumor suppressor in glioma and it suppresses glioma cell migration and invasion.(2)MOB2 regulates glioma cell migration and invasion via FAK/AKT signaling pathway.(3)MOB2 might be a novel potential target for glioma therapy...