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Induction of oxidative- and endoplasmic-reticulum-stress dependent apoptosis in pancreatic cancer cell lines by DDOST knockdown

The dolichyl-diphosphooligosaccharide-protein glycosyltransferase non-catalytic subunit (DDOST) is a key component of the oligosaccharyltransferase complex catalyzing N-linked glycosylation in the endoplasmic reticulum lumen. DDOST is associated with several cancers and congenital disorders of glyco...

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Main Authors: Böhme, Richard (Author) , Schmidt, Andreas W. (Author) , Hesselbarth, Nico (Author) , Posern, Guido (Author) , Sinz, Andrea (Author) , Ihling, Christian (Author) , Michl, Patrick (Author) , Laumen, Helmut (Author) , Rosendahl, Jonas (Author)
Format: Article (Journal)
Language:English
Published: 02 September 2024
In: Scientific reports
Year: 2024, Volume: 14, Pages: 1-13
ISSN:2045-2322
DOI:10.1038/s41598-024-68510-8
Online Access:Resolving-System, kostenfrei: https://doi.org/10.1038/s41598-024-68510-8
Resolving-System, kostenfrei: https://doi.org/10.25673/117103
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41598-024-68510-8
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Author Notes:Richard Böhme, Andreas W. Schmidt, Nico Hesselbarth, Guido Posern, Andrea Sinz, Christian Ihling, Patrick Michl, Helmut Laumen & Jonas Rosendahl
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Summary:The dolichyl-diphosphooligosaccharide-protein glycosyltransferase non-catalytic subunit (DDOST) is a key component of the oligosaccharyltransferase complex catalyzing N-linked glycosylation in the endoplasmic reticulum lumen. DDOST is associated with several cancers and congenital disorders of glycosylation. However, its role in pancreatic cancer remains elusive, despite its enriched pancreatic expression. Using quantitative mass spectrometry, we identify 30 differentially expressed proteins and phosphopeptides (DEPs) after DDOST knockdown in the pancreatic ductal adenocarcinoma (PDAC) cell line PA-TU-8988T. We evaluated DDOST / DEP protein-protein interaction networks using STRING database, correlation of mRNA levels in pancreatic cancer TCGA data, and biological processes annotated to DEPs in Gene Ontology database. The inferred DDOST regulated phenotypes were experimentally verified in two PDAC cell lines, PA-TU-8988T and BXPC-3. We found decreased proliferation and cell viability after DDOST knockdown, whereas ER-stress, ROS-formation and apoptosis were increased. In conclusion, our results support an oncogenic role of DDOST in PDAC by intercepting cell stress events and thereby reducing apoptosis. As such, DDOST might be a potential biomarker and therapeutic target for PDAC.
Item Description:Gesehen am 24.02.2025
Physical Description:Online Resource
ISSN:2045-2322
DOI:10.1038/s41598-024-68510-8

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