Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas
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...
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| Veröffentlicht in: | Oncotarget 2015-01, Vol.6 (3), p.1422-1434 |
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| creator | Costa, Angela Margarida Pinto, Filipe Martinho, Olga Oliveira, Maria José Jordan, Peter Reis, Rui Manuel |
| 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. |
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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.</description><identifier>EISSN: 1949-2553</identifier><identifier>PMID: 25596741</identifier><language>eng</language><publisher>United States</publisher><subject>Brain Neoplasms - enzymology ; Brain Neoplasms - genetics ; Brain Neoplasms - pathology ; Cell Line, Tumor ; Down-Regulation ; Gene Silencing ; Genes, Tumor Suppressor ; Glioma - enzymology ; Glioma - genetics ; Glioma - pathology ; Humans ; MAP Kinase Kinase 4 - biosynthesis ; MAP Kinase Kinase 4 - genetics ; MAP Kinase Kinase 4 - metabolism ; Matrix Metalloproteinase 2 - biosynthesis ; Matrix Metalloproteinase 2 - genetics ; Matrix Metalloproteinase 2 - metabolism ; Neoplasm Invasiveness ; Protein-Serine-Threonine Kinases - biosynthesis ; Protein-Serine-Threonine Kinases - genetics ; Transcriptional Activation ; Up-Regulation</subject><ispartof>Oncotarget, 2015-01, Vol.6 (3), p.1422-1434</ispartof><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25596741$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Costa, Angela Margarida</creatorcontrib><creatorcontrib>Pinto, Filipe</creatorcontrib><creatorcontrib>Martinho, Olga</creatorcontrib><creatorcontrib>Oliveira, Maria José</creatorcontrib><creatorcontrib>Jordan, Peter</creatorcontrib><creatorcontrib>Reis, Rui Manuel</creatorcontrib><title>Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><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.</description><subject>Brain Neoplasms - enzymology</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain Neoplasms - pathology</subject><subject>Cell Line, Tumor</subject><subject>Down-Regulation</subject><subject>Gene Silencing</subject><subject>Genes, Tumor Suppressor</subject><subject>Glioma - enzymology</subject><subject>Glioma - genetics</subject><subject>Glioma - pathology</subject><subject>Humans</subject><subject>MAP Kinase Kinase 4 - biosynthesis</subject><subject>MAP Kinase Kinase 4 - genetics</subject><subject>MAP Kinase Kinase 4 - metabolism</subject><subject>Matrix Metalloproteinase 2 - biosynthesis</subject><subject>Matrix Metalloproteinase 2 - genetics</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Neoplasm Invasiveness</subject><subject>Protein-Serine-Threonine Kinases - biosynthesis</subject><subject>Protein-Serine-Threonine Kinases - genetics</subject><subject>Transcriptional Activation</subject><subject>Up-Regulation</subject><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo1kEtLAzEUhYMgttT-BcnSzUDzbpZSfPahYMHlcJtJppGZzDiZIP77Rqxnc-85fJzFuUBTorkuqBBsguYxfi6yBFdLqq_QJMdaKk6myL37xgbjQ407h8ejxWNquwHH1PeDjTG_tQ0Wf-zWFPuIIUfGw2gr_O3HI06ZqlMDo-_Cb8N2-0YxhAq_7NbYB1w3vmshXqNLB0208_Odof3D_X71VGxeH59Xd5uiF5IUB0sOsARuDGNOKq2ZBEmAOCW0EkoYosVi4Qhl3FixdACOM1sZxrOvGGEzdPtX2w_dV7JxLFsfjW0aCLZLsSRSCEWp4DKjN2c0HVpblf3gWxh-yv9p2Akow18o</recordid><startdate>20150130</startdate><enddate>20150130</enddate><creator>Costa, Angela Margarida</creator><creator>Pinto, Filipe</creator><creator>Martinho, Olga</creator><creator>Oliveira, Maria José</creator><creator>Jordan, Peter</creator><creator>Reis, Rui Manuel</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20150130</creationdate><title>Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas</title><author>Costa, Angela Margarida ; 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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.</abstract><cop>United States</cop><pmid>25596741</pmid><tpages>13</tpages></addata></record> |
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| source | MEDLINE; PubMed Central Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free E- Journals |
| subjects | Brain Neoplasms - enzymology Brain Neoplasms - genetics Brain Neoplasms - pathology Cell Line, Tumor Down-Regulation Gene Silencing Genes, Tumor Suppressor Glioma - enzymology Glioma - genetics Glioma - pathology Humans MAP Kinase Kinase 4 - biosynthesis MAP Kinase Kinase 4 - genetics MAP Kinase Kinase 4 - metabolism Matrix Metalloproteinase 2 - biosynthesis Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 2 - metabolism Neoplasm Invasiveness Protein-Serine-Threonine Kinases - biosynthesis Protein-Serine-Threonine Kinases - genetics Transcriptional Activation Up-Regulation |
| title | Silencing of the tumor suppressor gene WNK2 is associated with upregulation of MMP2 and JNK in gliomas |
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