c-Src and Neural Wiskott-Aldrich Syndrome Protein (N-WASP) Promote Low Oxygen-Induced Accelerated Brain Invasion by Gliomas

摘要: Malignant gliomas remain associated with poor prognosis and high morbidity because of their ability to invade the brain; furthermore, human exhibit a phenotype accelerated brain invasion in response anti-angiogenic drugs. Here, we study 8 glioblastoma cell lines; U251, U87, D54 LN229 show motility low ambient oxygen. Src inhibition by Dasatinib abrogates this phenotype. Molecular discovery validation studies evaluate 46 molecules related or src pathway U251 cells. Demanding that molecular changes induced oxygen are reversed cells, identifies neural Wiskott-Aldrich syndrome protein (NWASP), Focal adhesion Kinase (FAK), -Catenin, Cofilin. However, only Src-mediated NWASP phosphorylation distinguishes four lines enhanced Downregulating c-Src RNA interference low-oxygen-induced enhancement vitro assays organotypic slice cultures. The findings support idea play key roles mediating pathogenesis oxygen-induced gliomas.