2. Academic Validation
  3. Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas

Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas

  • Oncotarget. 2015 Jan 30;6(3):1422-34. doi: 10.18632/oncotarget.2805.
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
Affiliations

Affiliations

  • 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.
PMID: 25596741 DOI: 10.18632/oncotarget.2805
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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