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Protein Kinase WNK2 has a Tumour Suppressor Role in Gliomas

dc.contributor.authorMoniz, Sonia
dc.contributor.authorMartinho, Olga
dc.contributor.authorPinto, Filipe
dc.contributor.authorReis, Rui Manuel
dc.contributor.authorJordan, Peter
dc.date.accessioned2012-10-24T14:43:40Z
dc.date.available2012-10-24T14:43:40Z
dc.date.issued2012-09-27
dc.description.abstractMalignant glioblastoma is the most common and lethal adult brain tumour type. Recently, the promoter region of the protein kinaseWNK2 gene was found to be hypermethylated in 29 of 31 infiltrative gliomas and about 5 of 7 meningiomas. We have previously described that theexperimental depletion of WNK2 expression decreases RhoA activity whilst leading to increased Rac1 activity. RhoA/Rac1 activities are important forcell migration and glioblastomas are very invasive tumours so that we tested the effects of WNK2 on wound-healing assays in glioma cell lines SW1088and A172. SW1088 cells express endogenous WNK2 and we observed that wound closure was increased upon experimental depletion of endogenousWNK2. In contrast, A172 cells display complete promoter region methylation and WNK2 re-expression was found to decrease migration. Consistently,we observed an increase in Rac1 activity in SW1088 cells upon WNK2 down-regulation, but lower levels of active Rac1 in A172 cells stably expressingWNK2 cDNA when compared with an equivalent cell line stably transfected with the same empty vector. Our studies indicate that loss of WNK2expression promotes Rac1 activation and may contribute to the highly invasive phenotype that glioblastomas present.por
dc.description.sponsorshipFundação para a Ciência e Tecnologiapor
dc.identifier.urihttp://hdl.handle.net/10400.18/1026
dc.language.isoporpor
dc.publisherInstituto Nacional de Saúde Doutor Ricardo Jorge, IPpor
dc.subjectVias de Transdução de Sinal e Patologias Associadaspor
dc.subjectWNK Protein Kinasespor
dc.subjectGliomapor
dc.subjectTumor Suppressorpor
dc.subjectInvasionpor
dc.subjectRac1por
dc.titleProtein Kinase WNK2 has a Tumour Suppressor Role in Gliomaspor
dc.typeconference object
dspace.entity.typePublication
oaire.citation.conferencePlaceOslo, Noruegapor
oaire.citation.titleFEBS workshop Dynamics of cell signal systems, 27-30 Sep 2012por
rcaap.rightsopenAccesspor
rcaap.typeconferenceObjectpor

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