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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 9, MAR 8 2019.
• Citações Web of Science: 1

Resumo

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)

• Processo FAPESP: 13/23271-0 - Análise funcional do remodelador de cromatina CHD7 em glioblastoma multiforme
• Beneficiário: Raquel Arminda Martinez Machado
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 14/21614-0 - Análise do papel do remodelador de cromatina CHD7 na manutenção e radioresistencia das células tronco tumorais em glioblastoma multiforme
• Beneficiário: Raquel Arminda Martinez Machado
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado