Open AccessREST Regulates Oncogenic Properties of Glioblastoma Stem Cells
Author(s) -
Kamal Mohamed M.,
Sathyan Pratheesh,
Singh Sanjay K.,
Zinn Pascal O.,
Marisetty Anantha L.,
Liang Shoudan,
Gumin Joy,
ElMesallamy Hala Osman,
Suki Dima,
Colman Howard,
Fuller Gregory N.,
Lang Frederick F.,
Majumder Sadhan
Publication year - 2012
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1020
Subject(s) - biology , gene knockdown , rest (music) , stem cell , repressor , cancer research , gene silencing , transcription factor , glioblastoma , apoptosis , microbiology and biotechnology , genetics , medicine , gene
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 REST‐expressing GSCs (HR‐GSCs) produced tumors histopathologically distinct from those generated by low REST‐expressing 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. S TEM C ELLS 2012;30:405–414