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Artigo Acesso aberto Produção Nacional
BIBTEX RIS

Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas

2014; Impact Journals LLC; Volume: 6; Issue: 3 Linguagem: Inglês

10.18632/oncotarget.2805

ISSN

1949-2553

Autores

Ângela M. Costa, Filipe Pinto, Olga Martinho, Maria José Oliveira, Peter Jordan, Rui Manuel Reis,

Tópico(s)

S100 Proteins and Annexins

Resumo

// Angela Margarida Costa 1, 2 , Filipe Pinto 1, 2 , Olga Martinho 1, 2 , Maria José Oliveira 3 , Peter Jordan 4, 5 , Rui Manuel Reis 1, 2, 6 1 ICVS-Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Campus Gualtar, Braga 4710-057, Portugal 2 ICVS/3B's - PT -Government Associate Laboratory, Braga/Guimarães 4710-057, Portugal 3 INEB-Institute of Biomedical Engineering, Porto 4150-180, Portugal 4 Department of Human Genetics, National Institute of Health Doutor Ricardo Jorge, Lisbon 1649-016, Portugal 5 BioFig-Center of Biodiversity, Functional and Integrative Genomics, Lisbon 1649-016, Portugal 6 Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, SP 14784-400, Brazil Correspondence to: Rui Manuel Reis, e-mail: rreis@ecsaude.uminho.pt Keywords: WNK2, MMP2, JNK, gliomas, invasion Received: July 16, 2014 Accepted: November 25, 2014 Published: December 22, 2014 ABSTRACT Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade extracellular matrix (ECM), thus assisting invasion. Upregulation of MMPs, frequently reported in gliomas, is associated with aggressive behavior. WNK2 is a tumor suppressor gene expressed in normal brain, and silenced by promoter methylation in gliomas. Patients without WNK2 exhibited poor prognosis, and its downregulation was associated with increased glioma cell invasion. Here we showed that MMP2 expression and activity are increased in glioma cell lines that do not express WNK2. Also, WNK2 inhibited JNK, a process associated with decreasing levels of MMP2. Thus, WNK2 promoter methylation and silencing in gliomas is associated with increased JNK activation and MMP2 expression and activity, thus explaining in part tumor cell invasion potential.

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