Silencing of the tumor suppressor gene 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/1822/62215
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 the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomasBrain NeoplasmsCell Line, TumorDown-RegulationGliomaHumansMAP Kinase Kinase 4Matrix Metalloproteinase 2Neoplasm InvasivenessProtein-Serine-Threonine KinasesTranscriptional ActivationUp-RegulationGene SilencingGenes, Tumor SuppressorMatrix 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.We thank Marta Oliveira for the GAPDH TaqMan probe for qRT-PCR, and Ana Pinto and Marta Laranjeiro Pinto for technical assistance. This work was supported by a Portuguese Foundation for Science and Technology (FCT) projects PTDC/SAU-TOX/114549/2009, and PTDC-SAUONC/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.2015-01-302015-01-30T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/62215eng10.18632/oncotarget.2805info: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:RCAAP2023-07-21T12:28:09Zoai:repositorium.sdum.uminho.pt:1822/62215Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:22:53.915318Repositório 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 the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas
spellingShingle Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas
Costa, Angela Margarida
Brain Neoplasms
Cell Line, Tumor
Down-Regulation
Glioma
Humans
MAP Kinase Kinase 4
Matrix Metalloproteinase 2
Neoplasm Invasiveness
Protein-Serine-Threonine Kinases
Transcriptional Activation
Up-Regulation
Gene Silencing
Genes, Tumor Suppressor
title_short Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title_full Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title_fullStr Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title_full_unstemmed Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas
title_sort Silencing of the tumor suppressor gene 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 Brain Neoplasms
Cell Line, Tumor
Down-Regulation
Glioma
Humans
MAP Kinase Kinase 4
Matrix Metalloproteinase 2
Neoplasm Invasiveness
Protein-Serine-Threonine Kinases
Transcriptional Activation
Up-Regulation
Gene Silencing
Genes, Tumor Suppressor
topic Brain Neoplasms
Cell Line, Tumor
Down-Regulation
Glioma
Humans
MAP Kinase Kinase 4
Matrix Metalloproteinase 2
Neoplasm Invasiveness
Protein-Serine-Threonine Kinases
Transcriptional Activation
Up-Regulation
Gene Silencing
Genes, Tumor Suppressor
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 2015-01-30
2015-01-30T00:00:00Z
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/1822/62215
url http://hdl.handle.net/1822/62215
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.18632/oncotarget.2805
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
repository.mail.fl_str_mv
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