Project description:Glioblastoma (GBM) is the most aggressive cancer in brain and contains a high mortality rate due to lack of effective treatment strategy. Molecular mechanisms of GBM characteristic invasive growth are urgently need to improve the poor prognosis.Here we reported that knockdown of GRIK1 retarded GBM cells growth and invasion.Moreover,high levels of GRIK1 were correlated to poor prognosis of GBM, consistent with The Cancer Genome Atlas (TCGA) database. Taken together, our study identified that GRIK1 is a novel and vital factor of GBM progression and may serve as a new biomarker for prognosis and therapy of GBM patients.
Project description:Co-amplification of EGFR and EGFRvIII, a tumor-specific truncation mutant of EGFR, represent hallmark genetic lesions in glioblastoma. We report that EGFR and EGFRvIII stimulate the innate immune defense receptor Toll-like Receptor 2 (TLR2); and that knockdown of TLR2 led to a dramatic survival advantage in glioblastoma xenografts. EGFR and EGFRvIII activated TLR2 in a ligand-independent manner, promoting tumor growth and immune evasion. We show that EGFR and EGFRvIII cooperate to activate the Rho-associated protein kinase ROCK2, modulating malignant progression both by activating TLR2 and WNT signaling, and through remodeling the tumor microenvironment.