Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming
Abstract Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in the pathobiology of myriad cancers, one of which is glioblastoma multiforme (GBM). As such,...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-07631-9 |
| _version_ | 1818845744860233728 |
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| author | Joshua D. Bernstock Daniel Ye Florian A. Gessler Yang-ja Lee Luca Peruzzotti-Jametti Peter Baumgarten Kory R. Johnson Dragan Maric Wei Yang Donat Kögel Stefano Pluchino John M. Hallenbeck |
| author_facet | Joshua D. Bernstock Daniel Ye Florian A. Gessler Yang-ja Lee Luca Peruzzotti-Jametti Peter Baumgarten Kory R. Johnson Dragan Maric Wei Yang Donat Kögel Stefano Pluchino John M. Hallenbeck |
| author_sort | Joshua D. Bernstock |
| collection | DOAJ |
| description | Abstract Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in the pathobiology of myriad cancers, one of which is glioblastoma multiforme (GBM). As such, the clinical significance and therapeutic utility offered via the selective control of global SUMOylation is readily apparent. There are, however, relatively few known/effective inhibitors of global SUMO-conjugation. Herein we describe the identification of topotecan as a novel inhibitor of global SUMOylation. We also provide evidence that inhibition of SUMOylation by topotecan is associated with reduced levels of CDK6 and HIF-1α, as well as pronounced changes in cell cycle progression and cellular metabolism, thereby highlighting its putative role as an adjuvant therapy in defined GBM patient populations. |
| first_indexed | 2024-12-19T05:34:32Z |
| format | Article |
| id | doaj.art-da4f8bc42ef147c6a124478a1b68ce27 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T05:34:32Z |
| publishDate | 2017-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-da4f8bc42ef147c6a124478a1b68ce272022-12-21T20:34:10ZengNature PortfolioScientific Reports2045-23222017-08-017111410.1038/s41598-017-07631-9Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programmingJoshua D. Bernstock0Daniel Ye1Florian A. Gessler2Yang-ja Lee3Luca Peruzzotti-Jametti4Peter Baumgarten5Kory R. Johnson6Dragan Maric7Wei Yang8Donat Kögel9Stefano Pluchino10John M. Hallenbeck11Stroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of HealthStroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of HealthWellcome Trust-Medical Research Council Stem Cell Institute, Department of Clinical Neurosciences, University of CambridgeStroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of HealthWellcome Trust-Medical Research Council Stem Cell Institute, Department of Clinical Neurosciences, University of CambridgeEdinger Institute, Johann Wolfgang Goethe-UniversitätBioinformatics Section, Information Technology & Bioinformatics Program, Division of Intramural Research (DIR), (NINDS/NIH)Flow Cytometry Core Facility, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NINDS/NIH)Department of Anesthesiology, Duke University Medical CenterDepartment of Neurosurgery, Johann Wolfgang Goethe-UniversitätWellcome Trust-Medical Research Council Stem Cell Institute, Department of Clinical Neurosciences, University of CambridgeStroke Branch, National Institute of Neurological Disorders and Stroke, National Institutes of HealthAbstract Protein SUMOylation is a dynamic post-translational modification shown to be involved in a diverse set of physiologic processes throughout the cell. SUMOylation has also been shown to play a role in the pathobiology of myriad cancers, one of which is glioblastoma multiforme (GBM). As such, the clinical significance and therapeutic utility offered via the selective control of global SUMOylation is readily apparent. There are, however, relatively few known/effective inhibitors of global SUMO-conjugation. Herein we describe the identification of topotecan as a novel inhibitor of global SUMOylation. We also provide evidence that inhibition of SUMOylation by topotecan is associated with reduced levels of CDK6 and HIF-1α, as well as pronounced changes in cell cycle progression and cellular metabolism, thereby highlighting its putative role as an adjuvant therapy in defined GBM patient populations.https://doi.org/10.1038/s41598-017-07631-9 |
| spellingShingle | Joshua D. Bernstock Daniel Ye Florian A. Gessler Yang-ja Lee Luca Peruzzotti-Jametti Peter Baumgarten Kory R. Johnson Dragan Maric Wei Yang Donat Kögel Stefano Pluchino John M. Hallenbeck Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming Scientific Reports |
| title | Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming |
| title_full | Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming |
| title_fullStr | Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming |
| title_full_unstemmed | Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming |
| title_short | Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming |
| title_sort | topotecan is a potent inhibitor of sumoylation in glioblastoma multiforme and alters both cellular replication and metabolic programming |
| url | https://doi.org/10.1038/s41598-017-07631-9 |
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