GRB2 Interacts With DEK To Regulates The Proliferation And Invasion Of Glioma Via The MEK/Erk/mTOR Pathway

Background:Glioma is the most common intracranial primary malignant tumor,which has the characteristics of strong proliferation and high invasiveness.The average survival time of glioblastoma(GBM)is only 14 months.In gliomas,growth factor receptor binding protein 2(GRB2)participates in the downstream regulation of cells after activation to promote the proliferation and invasion of gliomas.However,its regulation mechanism still needs extensive and in-depth research.Methods:RT-PCR,western blot and immunohistochemical(IHC)staining were conducted to investigate the potential role and prognostic value of GRB2 in glioma.Then GRB2 was stably overexpressed or knocked down in glioma cell lines.To further explore the potential biological function of GRB2 in glioma,cell counting kit-8(CCK-8)assays,colony formation assays,wound healing assays and transwell cell invasion assays were performed in vitro.Meanwhile,glioma subcutaneous xenograft tumor models were established for in vivo assays.Subsequently,immunoprecipitation(IP)and liquid chromatography coupled with tandem mass spectrometry(LC-MS/MS)analyses were applied to understand the molecular mechanisms of GRB2 in glioma.Co-IP was used to analyze the relationship between ribosomal protein DEK and GRB2.Finally,through in vitro cell function experiments,the interaction between DEK and GRB2 was verified.Results:GRB2 expression is up-regulated in gliomas,and is associated with a shorter overall survival period and a higher recurrence rate.In addition,the high expression of GRB2 is associated with clinical malignant pathological characteristics.In addition,the overexpression of GRB2 promotes the proliferation,invasion and apoptosis of glioma cells in vitro;promotes the growth of gliomas in vivo,and all these malignant characteristics are reduced with the knockdown of GRB2.In terms of mechanism,GRB2 is associated with DEK and promotes the mTOR signaling pathway.Conclusions:GRB2 interacts with DEK to regulate the proliferation,invasion and migration of gliomas through the MEK/Erk/mTOR signaling pathway,and GRB2 becomes a biomarker that can be used as a biomarker to assess the progression of gliomas.