MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility
Epigenetic silencing by DNA methylation in brain tumors has been reported for many genes, however, their function on pathogenesis needs to be evaluated. We investigated the MTSS1 gene, identified as hypermethylated by differential methylation hybridization (DMH). Fifty-nine glioma tissue samples and...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-02-01
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| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523316301334 |
| _version_ | 1818144891431026688 |
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| author | Daniel Luxen Gerrit H. Gielen Anke Waha Lukas Isselstein Tim Müller Philipp Koch Jennifer Hammes Albert Becker Matthias Simon Peter Wurst Elmar Endl Torsten Pietsch Marco Gessi Andreas Waha |
| author_facet | Daniel Luxen Gerrit H. Gielen Anke Waha Lukas Isselstein Tim Müller Philipp Koch Jennifer Hammes Albert Becker Matthias Simon Peter Wurst Elmar Endl Torsten Pietsch Marco Gessi Andreas Waha |
| author_sort | Daniel Luxen |
| collection | DOAJ |
| description | Epigenetic silencing by DNA methylation in brain tumors has been reported for many genes, however, their function on pathogenesis needs to be evaluated. We investigated the MTSS1 gene, identified as hypermethylated by differential methylation hybridization (DMH). Fifty-nine glioma tissue samples and seven glioma cell lines were examined for hypermethylation of the MTSS1 promotor, MTSS1 expression levels and gene dosage. GBM cell lines were treated with demethylating agents and interrogated for functional consequences of MTSS1 expression after transient transfection. Hypermethylation was significantly associated with IDH1/2 mutation. Comparative SNP analysis indicates higher incidence of loss of heterozygosity of MTSS1 in anaplastic astrocytomas and secondary glioblastomas as well as hypermethylation of the remaining allele. Reversal of promoter hypermethylation results in an increased MTSS1 expression. Cell motility was significantly inhibited by MTSS1 overexpression without influencing cell growth or apoptosis. Immunofluorescence analysis of MTSS1 in human astrocytes indicates co-localization with actin filaments. MTSS1 is down-regulated by DNA methylation in glioblastoma cell lines and is part of the G-CIMP phenotype in primary glioma tissues. Our data on normal astrocytes suggest a function of MTSS1 at focal contact structures with an impact on migratory capacity but no influence on apoptosis or cellular proliferation. |
| first_indexed | 2024-12-11T11:54:46Z |
| format | Article |
| id | doaj.art-fb95047bfcd8439eb144bccce06fe7a7 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 1944-7124 |
| language | English |
| last_indexed | 2024-12-11T11:54:46Z |
| publishDate | 2017-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-fb95047bfcd8439eb144bccce06fe7a72022-12-22T01:08:16ZengElsevierTranslational Oncology1936-52331944-71242017-02-01101707910.1016/j.tranon.2016.11.006MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motilityDaniel Luxen0Gerrit H. Gielen1Anke Waha2Lukas Isselstein3Tim Müller4Philipp Koch5Jennifer Hammes6Albert Becker7Matthias Simon8Peter Wurst9Elmar Endl10Torsten Pietsch11Marco Gessi12Andreas Waha13Department of Neuropathology, University of Bonn, GermanyDepartment of Neuropathology, University of Bonn, GermanyDepartment of Neuropathology, University of Bonn, GermanyDepartment of Neuropathology, University of Bonn, GermanyDepartment of Neuropathology, University of Bonn, GermanyInstitute of Reconstructive Neurobiology, LIFE & BRAIN, University of Bonn, GermanyDepartment of Neuropathology, University of Bonn, GermanyDepartment of Neuropathology, University of Bonn, GermanyInstitute of Neurosurgery, University of Bonn, GermanyDepartment of Molecular Medicine and Experimental Immunology, (Core Facility Flow Cytometry) University of Bonn, GermanyDepartment of Molecular Medicine and Experimental Immunology, (Core Facility Flow Cytometry) University of Bonn, GermanyDepartment of Neuropathology, University of Bonn, GermanyDepartment of Neuropathology, University of Bonn, GermanyDepartment of Neuropathology, University of Bonn, GermanyEpigenetic silencing by DNA methylation in brain tumors has been reported for many genes, however, their function on pathogenesis needs to be evaluated. We investigated the MTSS1 gene, identified as hypermethylated by differential methylation hybridization (DMH). Fifty-nine glioma tissue samples and seven glioma cell lines were examined for hypermethylation of the MTSS1 promotor, MTSS1 expression levels and gene dosage. GBM cell lines were treated with demethylating agents and interrogated for functional consequences of MTSS1 expression after transient transfection. Hypermethylation was significantly associated with IDH1/2 mutation. Comparative SNP analysis indicates higher incidence of loss of heterozygosity of MTSS1 in anaplastic astrocytomas and secondary glioblastomas as well as hypermethylation of the remaining allele. Reversal of promoter hypermethylation results in an increased MTSS1 expression. Cell motility was significantly inhibited by MTSS1 overexpression without influencing cell growth or apoptosis. Immunofluorescence analysis of MTSS1 in human astrocytes indicates co-localization with actin filaments. MTSS1 is down-regulated by DNA methylation in glioblastoma cell lines and is part of the G-CIMP phenotype in primary glioma tissues. Our data on normal astrocytes suggest a function of MTSS1 at focal contact structures with an impact on migratory capacity but no influence on apoptosis or cellular proliferation.http://www.sciencedirect.com/science/article/pii/S1936523316301334 |
| spellingShingle | Daniel Luxen Gerrit H. Gielen Anke Waha Lukas Isselstein Tim Müller Philipp Koch Jennifer Hammes Albert Becker Matthias Simon Peter Wurst Elmar Endl Torsten Pietsch Marco Gessi Andreas Waha MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility Translational Oncology |
| title | MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility |
| title_full | MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility |
| title_fullStr | MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility |
| title_full_unstemmed | MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility |
| title_short | MTSS1 is epigenetically regulated in glioma cells and inhibits glioma cell motility |
| title_sort | mtss1 is epigenetically regulated in glioma cells and inhibits glioma cell motility |
| url | http://www.sciencedirect.com/science/article/pii/S1936523316301334 |
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