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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

CHD7 promotes glioblastoma cell motility and invasiveness through transcriptional modulation of an invasion signature

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Author(s):
Machado, Raquel A. C. [1, 2] ; Schneider, Hannah [3, 4] ; Deocesano-Pereira, Carlos [5, 1] ; Lichtenstein, Flavio [5] ; Andrade, Fernando [6] ; Fujita, Andre [6] ; Trombetta-Lima, Marina [1] ; Weller, Michael [3, 4] ; Bowman-Colin, Christian [1, 7] ; Sogayar, Mari Cleide [1, 2]
Total Authors: 10
Affiliation:
[1] Univ Sao Paulo, Cell & Mol Therapy Ctr NUCEL, Internal Med Dept, Sch Med, BR-05360130 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Dept Biochem, Chem Inst, BR-05508000 Sao Paulo, SP - Brazil
[3] Univ Zurich, Zurich - Switzerland
[4] Univ Hosp, Lab Mol Neurooncol, Dept Neurol, Zurich - Switzerland
[5] CENTD, Butantan Inst, Sao Paulo, SP - Brazil
[6] Univ Sao Paulo, Dept Comp Sci, Inst Math & Stat, Sao Paulo - Brazil
[7] Harvard Med Sch, Dana Farber Canc Inst, 1 Jimmi Fund Way SM808, Boston, MA 02115 - USA
Total Affiliations: 7
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 9, MAR 8 2019.
Web of Science Citations: 0
Abstract

Chromatin remodeler proteins exert an important function in promoting dynamic modifications in the chromatin architecture, performing a central role in regulating gene transcription. Deregulation of these molecular machines may lead to striking perturbations in normal cell function. The CHD7 gene is a member of the chromodomain helicase DNA-binding family and, when mutated, has been shown to be the cause of the CHARGE syndrome, a severe developmental human disorder. Moreover, CHD7 has been described to be essential for neural stem cells and it is also highly expressed or mutated in a number of human cancers. However, its potential role in glioblastoma has not yet been tested. Here, we show that CHD7 is up-regulated in human glioma tissues and we demonstrate that CHD7 knockout (KO) in LN-229 glioblastoma cells suppresses anchorage-independent growth and spheroid invasion in vitro. Additionally, CHD7 KO impairs tumor growth and increases overall survival in an orthotopic mouse xenograft model. Conversely, ectopic overexpression of CHD7 in LN-428 and A172 glioblastoma cell lines increases cell motility and invasiveness in vitro and promotes LN-428 tumor growth in vivo. Finally, RNA-seq analysis revealed that CHD7 modulates a specific transcriptional signature of invasion-related target genes. Further studies should explore clinical-translational implications for glioblastoma treatment. (AU)

FAPESP's process: 13/23271-0 - Role of the CHD7 chromatin remodeler protein in human brain tumor cells
Grantee:Raquel Arminda Carvalho Machado
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 14/21614-0 - Role of CHD7 chromatin remodeler protein in glioblastoma stem cells (GSCs) maintenance and radioresistance
Grantee:Raquel Arminda Carvalho Machado
Support type: Scholarships abroad - Research Internship - Doctorate