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

2015-01Journal article Open access
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dc.contributor.authorCosta, Ângela
dc.contributor.authorPinto, Filipe
dc.contributor.authorMartinho, Olga
dc.contributor.authorOliveira, Maria José
dc.contributor.authorJordan, Peter
dc.contributor.authorReis, Rui Manuel
dc.date.accessioned2016-02-19T12:15:44Z
dc.date.available2016-02-19T12:15:44Z
dc.date.issued2015-01
dc.descriptionFree PMC Article: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4359304/pt_PT
dc.description.abstractMatrix 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.pt_PT
dc.description.sponsorshipThis 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.pt_PT
dc.identifier.citationOncotarget. 2015 Jan 30;6(3):1422-34. doi: 10.18632/oncotarget.2805pt_PT
dc.identifier.doi10.18632/oncotarget.2805pt_PT
dc.identifier.issn1949-2553
dc.identifier.urihttp://hdl.handle.net/10400.18/3437
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherImpact Journals, LLCpt_PT
dc.relationPotential predictive biomarkers of anti-RTKs therapy response in gliomas: An “in vitro” and “in vivo” Study
dc.relationEffect of radio- and chemotherapy on cancer cell invasion: the role of macrophages
dc.relation.publisherversionhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=2805&pubmed-linkout=1pt_PT
dc.subjectVias de Transdução de Sinal e Patologias Associadaspt_PT
dc.subjectGliomapt_PT
dc.subjectWNK2pt_PT
dc.subjectMMP2pt_PT
dc.subjectJNKpt_PT
dc.subjectTumor Suppressorpt_PT
dc.titleSilencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomaspt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitlePotential predictive biomarkers of anti-RTKs therapy response in gliomas: An “in vitro” and “in vivo” Study
oaire.awardTitleEffect of radio- and chemotherapy on cancer cell invasion: the role of macrophages
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-TOX%2F114549%2F2009/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/5876-PPCDTI/PTDC%2FSAU-ONC%2F112511%2F2009/PT
oaire.citation.endPage1434pt_PT
oaire.citation.startPage1422pt_PT
oaire.citation.titleOncotargetpt_PT
oaire.citation.volume6(3)pt_PT
oaire.fundingStream5876-PPCDTI
oaire.fundingStream5876-PPCDTI
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isProjectOfPublicationa48d73e5-e4a2-435d-8f59-8fead7ade239
relation.isProjectOfPublication1492f4b5-16f3-4327-9519-128e4b1590ec
relation.isProjectOfPublication.latestForDiscoverya48d73e5-e4a2-435d-8f59-8fead7ade239

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