Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming.
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Authors
Ye, Daniel
Lee, Yang-Ja
Baumgarten, Peter
Johnson, Kory R
Maric, Dragan
Yang, Wei
Kögel, Donat
Hallenbeck, John M
Publication Date
2017-08-07Journal Title
Scientific Reports
ISSN
2045-2322
Publisher
Nature Publishing Group
Volume
7
Issue
1
Pages
7425-7425
Language
eng
Type
Article
This Version
VoR
Metadata
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Bernstock, J., Ye, D., Gessler, F., Lee, Y., Peruzzotti Jametti, L., Baumgarten, P., Johnson, K. R., et al. (2017). Topotecan is a potent inhibitor of SUMOylation in glioblastoma multiforme and alters both cellular replication and metabolic programming.. Scientific Reports, 7 (1), 7425-7425. https://doi.org/10.1038/s41598-017-07631-9
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.
Keywords
cancer, cancer therapy
Sponsorship
This work was supported by the Intramural Research Program of the NINDS/NIH and a core support grant from the Wellcome Trust and Medical Research Council to the Wellcome Trust – MRC Cambridge Stem Cell Institute. Additionally, JDB is supported by a NIH-OxCam Fellowship and FAG is supported by a scholarship from the Gates Cambridge Trust. The authors wish to acknowledge the assistance of Dr. Yan Li of the NINDS/NIH Proteomics Core.
Funder references
MRC (MC_PC_12009)
Identifiers
External DOI: https://doi.org/10.1038/s41598-017-07631-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/270096
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