AI Article Synopsis
- The DDOST protein is crucial for the N-linked glycosylation process in the endoplasmic reticulum and is linked to various cancers and congenital glycosylation disorders.
- Research shows that knocking down DDOST expression in pancreatic cancer cells (specifically PDAC) leads to changes in protein expression and interactions, pointing to its potential role in the disease.
- Results indicate that DDOST knockdown decreases cancer cell proliferation and viability while increasing stress responses and apoptosis, suggesting that DDOST may act as an oncogene and could be targeted for therapeutic strategies in pancreatic cancer.
Article 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369111 | PMC |
| http://dx.doi.org/10.1038/s41598-024-68510-8 | DOI Listing |
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