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Author (up) Hu, B.; Emdad, L.; Kegelman, T.P.; Shen, X.-N.; Das, S.K.; Sarkar, D.; Fisher, P.B. url  doi
  Title Astrocyte Elevated Gene-1 Regulates beta-Catenin Signaling to Maintain Glioma Stem-like Stemness and Self-Renewal Type Journal Article
  Year 2017 Publication Molecular Cancer Research : MCR Abbreviated Journal Mol Cancer Res  
  Volume 15 Issue 2 Pages 225-233  
  Keywords Brain Neoplasms/genetics/metabolism/*pathology; Cell Adhesion Molecules/genetics/*metabolism; Cell Line, Tumor; Glioblastoma/genetics/metabolism/*pathology; Humans; Neoplastic Stem Cells/*pathology; Signal Transduction; Tumor Cells, Cultured; beta Catenin/genetics/*metabolism  
  Abstract Glioblastoma multiforme is a common malignant brain tumor that portends extremely poor patient survival. Recent studies reveal that glioma stem-like cells (GSC) are responsible for glioblastoma multiforme escape from chemo-radiotherapy and mediators of tumor relapse. Previous studies suggest that AEG-1 (MTDH), an oncogene upregulated in most types of cancers, including glioblastoma multiforme, plays a focal role linking multiple signaling pathways in tumorigenesis. We now report a crucial role of AEG-1 in glioma stem cell biology. Primary glioblastoma multiforme cells were isolated from tumor specimens and cultured as neurospheres. Using the surface marker CD133, negative and positive cells were separated as nonstem and stem populations by cell sorting. Tissue samples and low passage cells were characterized and compared with normal controls. Functional biological assays were performed to measure stemness, self-renewal, differentiation, adhesion, protein-protein interactions, and cell signaling. AEG-1 was upregulated in all glioblastoma multiforme neurospheres compared with normal neural stem cells. Expression of AEG-1 was strongly associated with stem cell markers CD133 and SOX2. AEG-1 facilitated beta-catenin translocation into the nucleus by forming a complex with LEF1 and beta-catenin, subsequently activating Wnt signaling downstream genes. Through an AEG-1/Akt/GSK3beta signaling axis, AEG-1 controlled phosphorylation levels of beta-catenin that stabilized the protein. IMPLICATIONS: This study discovers a previously unrecognized role of AEG-1 in GSC biology and supports the significance of this gene as a potential therapeutic target for glioblastoma multiforme. Mol Cancer Res; 15(2); 225-33. (c)2016 AACR.  
  Address VCU Massey Cancer Center, School of Medicine, Virginia Commonwealth University, Richmond, Virginia  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1541-7786 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27903708 Approved no  
  Call Number ref @ user @ Serial 96619  
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