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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
REST regulates oncogenic properties of glioblastoma stem cells
Stem Cells, Volume 30, No. 3, Year 2012
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Description
Glioblastoma multiforme (GBM) tumors are the most common malignant primary brain tumors in adults. Although many GBM tumors are believed to be caused by self-renewing, glioblastoma-derived stem-like cells (GSCs), the mechanisms that regulate self-renewal and other oncogenic properties of GSCs are only now being unraveled. Here we showed that GSCs derived from GBM patient specimens express varying levels of the transcriptional repressor repressor element 1 silencing transcription factor (REST), suggesting heterogeneity across different GSC lines. Loss- and gain-of-function experiments indicated that REST maintains self-renewal of GSCs. High RESTexpressing GSCs (HR-GSCs) produced tumors histopathologically distinct from those generated by low RESTexpressing GSCs (LR-GSCs) in orthotopic mouse brain tumor models. Knockdown of REST in HR-GSCs resulted in increased survival in GSC-transplanted mice and produced tumors with higher apoptotic and lower invasive properties. Conversely, forced expression of exogenous REST in LR-GSCs produced decreased survival in mice and produced tumors with lower apoptotic and higher invasive properties, similar to HR-GSCs. Thus, based on our results, we propose that a novel function of REST is to maintain self-renewal and other oncogenic properties of GSCs and that REST can play a major role in mediating tumorigenicity in GBM. © AlphaMed Press.
Authors & Co-Authors
Kamal, Mohamed Mostafa
United States, Houston
The University of Texas Md Anderson Cancer Center
Egypt, Cairo
Faculty of Pharmacy - Ain Shams University
Sathyan, Pratheesh
United States, Houston
The University of Texas Md Anderson Cancer Center
Singh, Sanjay K.
United States, Houston
The University of Texas Md Anderson Cancer Center
Zinn, Pascal O.
United States, Houston
The University of Texas Md Anderson Cancer Center
Switzerland, Lausanne
Centre Hospitalier Universitaire Vaudois
Marisetty, Anantha
United States, Houston
The University of Texas Md Anderson Cancer Center
Liang, Shoudan
United States, Houston
The University of Texas Md Anderson Cancer Center
Gumin, Joy
United States, Houston
The University of Texas Md Anderson Cancer Center
El-Mesallamy, Hala Osman
Egypt, Cairo
Faculty of Pharmacy - Ain Shams University
Suki, Dima
United States, Houston
The University of Texas Md Anderson Cancer Center
Colman, Howard
United States, Houston
The University of Texas Md Anderson Cancer Center
Fuller, Gregory N.
United States, Houston
The University of Texas Md Anderson Cancer Center
Lang, Frederick F.
United States, Houston
The University of Texas Md Anderson Cancer Center
Majumder, Sadhan
United States, Houston
The University of Texas Md Anderson Cancer Center
United States, Houston
University of Texas Graduate School of Biomedical Sciences at Houston
Statistics
Citations: 74
Authors: 13
Affiliations: 4
Identifiers
Doi:
10.1002/stem.1020
ISSN:
10665099
Research Areas
Cancer
Genetics And Genomics
Health System And Policy