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O-GlcNAc Transferase Inhibition Differentially Affects Breast Cancer Subtypes

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dc.contributor.author Barkovskaya, Anna
dc.contributor.author Seip, Kotryna
dc.contributor.author Hilmarsdóttir, Bylgja
dc.contributor.author Maelandsmo, Gunhild M
dc.contributor.author Moestue, Siver A
dc.contributor.author Itkonen, Harri M
dc.date.accessioned 2022-12-24T01:06:09Z
dc.date.available 2022-12-24T01:06:09Z
dc.date.issued 2019-04-05
dc.identifier.citation Barkovskaya , A , Seip , K , Hilmarsdóttir , B , Maelandsmo , G M , Moestue , S A & Itkonen , H M 2019 , ' O-GlcNAc Transferase Inhibition Differentially Affects Breast Cancer Subtypes ' , Scientific Reports , vol. 9 , no. 1 , pp. 5670 . https://doi.org/10.1038/s41598-019-42153-6
dc.identifier.issn 2045-2322
dc.identifier.other 69386279
dc.identifier.other 4755968e-1865-4b6c-be4b-310b683ee48a
dc.identifier.other 30952976
dc.identifier.other PubMedCentral: PMC6450885
dc.identifier.other 85064054924
dc.identifier.uri https://hdl.handle.net/20.500.11815/3793
dc.description.abstract Post-translational modification of intracellular proteins with a single N-acetylglucosamine sugar (O-GlcNAcylation) regulates signaling, proliferation, metabolism and protein stability. In breast cancer, expression of the enzyme that catalyzes O-GlcNAcylation - O-GlcNAc-transferase (OGT), and the extent of protein O-GlcNAcylation, are upregulated in tumor tissue, and correlate with cancer progression. Here we compare the significance of O-GlcNAcylation in a panel of breast cancer cells of different phenotypes. We find a greater dependency on OGT among triple-negative breast cancer (TNBC) cell lines, which respond to OGT inhibition by undergoing cell cycle arrest and apoptosis. Searching for the cause of this response, we evaluate the changes in the proteome that occur after OGT inhibition or knock-down, employing a reverse-phase protein array (RPPA). We identify transcriptional repressor - hairy and enhancer of split-1 (HES1) - as a mediator of the OGT inhibition response in the TNBC cells. Inhibition of OGT as well as the loss of HES1 results in potent cytotoxicity and apoptosis. The study raises a possibility of using OGT inhibition to potentiate DNA damage in the TNBC cells.
dc.format.extent 5646818
dc.format.extent 5670
dc.language.iso en
dc.relation.ispartofseries Scientific Reports; 9(1)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Náttúrufræðingar
dc.subject Apoptosis/physiology
dc.subject Cell Cycle Checkpoints/physiology
dc.subject Cell Line, Tumor
dc.subject DNA Damage/physiology
dc.subject Female
dc.subject Humans
dc.subject N-Acetylglucosaminyltransferases/metabolism
dc.subject Transcription Factor HES-1/metabolism
dc.subject Triple Negative Breast Neoplasms/metabolism
dc.subject Up-Regulation/physiology
dc.title O-GlcNAc Transferase Inhibition Differentially Affects Breast Cancer Subtypes
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.doi 10.1038/s41598-019-42153-6
dc.contributor.department Clinical Laboratory Services, Diagnostics and Blood Bank

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