Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/1132
Título: Loss of WNK2 expression by promoter gene methylation occurs in adult gliomas and triggers Rac1-mediated tumour cell invasiveness
Autor: Moniz, Sónia
Martinho, Olga
Pinto, Filipe
Sousa, Bárbara
Loureiro, Cláudia
Oliveira, Maria José
Moita, Luís Ferreira
Honavar, Mrinalini
Pinheiro, Célia
Pires, Manuel
Lopes, José Manuel
Jones, Chris
Costello, Joseph F
Paredes, Joana
Reris, Rui Manuel
Jordan, Peter
Palavras-chave: Vias de Transdução de Sinal e Patologias Associadas
Glioma
WNK
Rac1
Invasion
Promoter Methylation
Epigenetic
Data: Jan-2013
Editora: Oxford University Press
Citação: Hum Mol Genet. 2013 Jan 1;22(1):84-95
Resumo: The gene encoding protein kinase WNK2 was recently identified to be silenced by promoter hypermethylation in gliomas and meningiomas, suggesting a tumour-suppressor role in these brain tumours. Following experimental depletion in cell lines, WNK2 was further found to control GTP-loading of Rac1, a signalling guanosine triphosphatase involved in cell migration and motility. Here we show that WNK2 promoter methylation also occurs in 17.5% (29 out of 166) of adult gliomas, whereas it is infrequent in its paediatric forms (1.6%; 1 out of 66). Re-expression of WNK2 in glioblastoma cells presenting WNK2 gene silencing reduced cell proliferation in vitro, tumour growth in vivo and also cell migration and invasion, an effect correlated with reduced activation of Rac1. In contrast, when endogenous WNK2 was depleted from glioblastoma cells with unmethylated WNK2 promoter, changes in cell morphology, an increase in invasion and activation of Rac1 were observed. Together, these results validate the WNK2 gene as a recurrent target for epigenetic silencing in glia-derived brain tumours and provide first mechanistic evidence for a tumour-suppressing role of WNK2 that is related to Rac1 signalling and tumour cell invasion and proliferation.
Peer review: yes
URI: http://hdl.handle.net/10400.18/1132
ISSN: 0964-6906
Versão do Editor: http://hmg.oxfordjournals.org/content/22/1/84.abstract
Aparece nas colecções:DGH - Artigos em revistas internacionais

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