2. Academic Validation
  3. Induction of oxidative- and endoplasmic-reticulum-stress dependent apoptosis in pancreatic cancer cell lines by DDOST knockdown

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

  • Sci Rep. 2024 Sep 2;14(1):20388. doi: 10.1038/s41598-024-68510-8.
Richard Böhme 1,  Andreas W Schmidt 2 3 4,  Nico Hesselbarth 2,  Guido Posern 5,  Andrea Sinz 6,  Christian Ihling 5,  Patrick Michl 2 7,  Helmut Laumen 8,  Jonas Rosendahl 2
Affiliations

Affiliations

  • 1 Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany. richard_boehme@web.de.
  • 2 Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
  • 3 Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, Tübingen, Germany.
  • 4 Paediatric Nutritional Medicine, Else Kröner Fresenius Center for Nutritional Medicine, Technical University of Munich (TUM), Freising, Germany.
  • 5 Institute for Physiological Chemistry, Medical Faculty, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
  • 6 Department of Pharmaceutical Chemistry and Bioanalytics, Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
  • 7 Department of Internal Medicine IV, Heidelberg University, University Hospital Heidelberg, Heidelberg, Germany.
  • 8 Department of Internal Medicine I, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany. helmut.laumen@medizin.uni-halle.de.
PMID: 39223141 DOI: 10.1038/s41598-024-68510-8
Abstract

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.

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