ArticleMolecular cancer2015
COSMC knockdown mediated aberrant O-glycosylation promotes oncogenic properties in pancreatic cancer.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 123 citations in OpenAlex.
- Distinct glycosyltransferase expression governs organ-specific survival in pancreatic cancer metastasis.Oncogene · 2026Article
- GALNT7 promotes the malignant progression of gastrointestinal stromal tumors by regulating KIT O-GalNAc glycosylation.Precision clinical medicine · 2026Article
- Tumor glycosylation engages CD301b-mediated myeloid regulation in breast cancer.Research square · 2026Article
- Deletion of Core 1 β3GalT-specific molecular chaperone (Cosmc) in murine intestinal epithelia leads to major alterations in glycocalyx and tumorigenesis.The Journal of biological chemistry · 2026Article
- Treatment of acute myeloid leukemia models by targeting a cell surface RNA-binding protein.Nature biotechnology · 2026Article
- LncSLED1 inhibits monosodium urate-induced macrophage inflammation by promoting Cosmc methylation to upregulate CA72-4.Central-European journal of immunology · 2026Article
- CD301b lectin expression in the breast tumor microenvironment augments tumor growth.Research square · 2025Article
- CD301b lectin expression in the breast tumor microenvironment augments tumor growth.bioRxiv : the preprint server for biology · 2025Article
- Unraveling the glyco-immunity nexus in pancreatic cancer.Molecular cancer · 2025Review
- Glycoproteomics of Gastrointestinal Cancers and Its Use in Clinical Diagnostics.Journal of proteome research · 2025Review
- Article
- Overexpression of Tn antigen induces chronic pancreatitis in mice.Scientific reports · 2025Article
- Multilevel plasticity and altered glycosylation drive aggressiveness in hypoxic and glucose-deprived bladder cancer cells.iScience · 2025Article
- Tumor-associated Tn and STn antigens: from molecular mechanism to precision diagnosis and treatment.Frontiers in immunology · 2025Review
- Targeting Tn Antigen Suppresses Aberrant O-Glycosylation-Elicited Metastasis in Breast Cancer.Journal of cellular and molecular medicine · 2024Article
- GalNT2-mediated O-glycosylation affects pancreas development and function in mice.Scientific reports · 2024Article
- Substrate O-glycosylation actively regulates extracellular proteolysis.Protein science : a publication of the Protein Society · 2024Article
- MOTAI: A Novel Method for the Study of O-GalNAcylation and Complex O-Glycosylation in Cancer.Analytical chemistry · 2024Article
- CCDC88C, an O-GalNAc glycosylation substrate of GALNT6, drives breast cancer metastasis by promoting c-JUN-mediated CEMIP transcription.Cancer cell international · 2024Article
- A Comprehensive Analysis of Tn and STn Antigen Expression in Esophageal Adenocarcinoma.Cancers · 2024Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHuman pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies in the world and despite great efforts in research types of treatment remain limited. A frequently detected alteration in PDACs is a truncated O-linked N-acetylgalactosamine (GalNAc) glycosylation with expression of the Tn antigen. Changes in O-glycosylation affect posttranslationally modified O-GalNAc proteins resulting in profound cellular alterations. Tn antigen is a tumor associated glycan detected in 75-90 % of PDACs and up to 67 % in its precursor lesions. Since the role of Tn antigen expression in PDAC is insufficiently understood we analyzed the impact of COSMC mediated Tn antigen expression in two human PDAC cell lines on cellular oncogenic properties.
methodsForced expression of Tn antigen on O-glycosylated proteins in pancreatic cancer cells was induced by lentiviral-mediated knockdown of the COSMC chaperone, which prevented O-glycan elongation beyond the initial GalNAcα1- residue on O-linked glycoproteins. Altered O-GalNAc glycosylation was analyzed in human pancreatic cancer cell lines Panc-1 and L3.6pl using Western and Far-Western blot as well as immunocytochemical techniques. To assess the biological implications of COSMC function on oncogenic properties, cell viability assays, scratch assays combined with live cell imaging, migration and apoptosis assays were performed. Lectin based glycoprotein enrichment with subsequent mass spectrometric analysis identified new cancer O-GalNAc modified proteins. Expression of Tn antigen bearing Nucleolin in patient derived PDAC tumor specimens was evaluated and correlated with clinicopathological data.
resultsTn antigen expression was induced on various O-GalNAc glycoproteins in COSMC deficient cell lines compared to the control. Proliferation was reduced (p < 0.001) in COSMC knockdown cells, whereas migration was increased (p < 0.001) and apoptosis was decreased (p = 0.03), highlighting the importance of Tn antigen expression on metastatic and anti-apoptotic behavior of PDAC derived cells. Nucleolin was identified as O-GalNAc modified protein in COSMC deficient PDAC cell lines. Interestingly, immunohistochemical staining and co-localization studies of patient derived PDACs revealed poor survival for patients with strong co-localization of Tn antigen and Nucleolin (p = 0.037).
conclusionThis study substantiates the influence of altered O-glycan (Tn/STn) expression on oncogenic properties in pancreatic cancer and identifies O-GalNAc modified Nucleolin as novel prognostic marker.
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