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

Detalhes bibliográficos
Autor(a) principal: Costa, Angela Margarida
Data de Publicação: 2015
Outros Autores: Pinto, Filipe, Martinho, Olga, Oliveira, Maria José, Jordan, Peter, Reis, R. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/1822/32853
Resumo: 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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spelling Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomasWNK2MMP2JNKGliomasInvasionScience & TechnologyMatrix 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.This work was supported by a Portuguese Foundation for Science and Technology (FCT) projects PTDC/SAU-TOX/114549/2009, and PTDC-SAU-ONC/112511/2009. AMC is a Post-doc Fellow (PTDC/SAU-TOX/114549/2009), and FP is a PhD Fellow (SFRH/BD/81369/2011) from FCT. OM is a Post-doc Fellow from QREN (UMINHO/BPD/32/2013). MJO is an Investigator FCT recipient.Impact JournalsUniversidade do MinhoCosta, Angela MargaridaPinto, FilipeMartinho, OlgaOliveira, Maria JoséJordan, PeterReis, R. M.20152015-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/32853eng1949-255325596741http://www.impactjournals.com/oncotarget/index.php?journal=oncotargetinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:33:06Zoai:repositorium.sdum.uminho.pt:1822/32853Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:28:33.932352Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas
spellingShingle Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas
Costa, Angela Margarida
WNK2
MMP2
JNK
Gliomas
Invasion
Science & Technology
title_short Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title_full Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title_fullStr Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title_full_unstemmed Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title_sort Silencing of WNK2 is associated with upregulation of MMP2 and JNK in gliomas
author Costa, Angela Margarida
author_facet Costa, Angela Margarida
Pinto, Filipe
Martinho, Olga
Oliveira, Maria José
Jordan, Peter
Reis, R. M.
author_role author
author2 Pinto, Filipe
Martinho, Olga
Oliveira, Maria José
Jordan, Peter
Reis, R. M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Universidade do Minho
dc.contributor.author.fl_str_mv Costa, Angela Margarida
Pinto, Filipe
Martinho, Olga
Oliveira, Maria José
Jordan, Peter
Reis, R. M.
dc.subject.por.fl_str_mv WNK2
MMP2
JNK
Gliomas
Invasion
Science & Technology
topic WNK2
MMP2
JNK
Gliomas
Invasion
Science & Technology
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/1822/32853
url http://hdl.handle.net/1822/32853
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1949-2553
25596741
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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