Astrocyte Elevated Gene-1 Regulates β-Catenin Signaling to Maintain Glioma Stem-like Stemness and Self-Renewal.

摘要: Glioblastoma multiforme is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal glioma stem-like cells (GSC) are responsible for glioblastoma escape from chemo-radiotherapy and mediators of relapse. Previous suggest AEG-1 (MTDH), an oncogene upregulated in most types cancers, including multiforme, plays focal role linking multiple signaling pathways tumorigenesis. We now report crucial stem cell biology. Primary were isolated specimens cultured as neurospheres. Using the surface marker CD133, negative positive separated nonstem populations by sorting. Tissue samples low passage characterized compared with normal controls. Functional biological assays performed to measure stemness, self-renewal, differentiation, adhesion, protein–protein interactions, signaling. was all neurospheres neural cells. Expression strongly associated markers CD133 SOX2. facilitated β-catenin translocation into nucleus forming complex LEF1 β-catenin, subsequently activating Wnt downstream genes. Through AEG-1/Akt/GSK3β axis, controlled phosphorylation levels stabilized protein. Implications: This study discovers previously unrecognized GSC biology supports significance this gene potential therapeutic target multiforme. Mol Cancer Res; 15(2); 225–33. ©2016 AACR.