Aberrant expression of Sialyl-Tn (STn) antigen correlates with poor prognosis and reduced patient survival. We demonstrated that expression of Tn and STn in pancreatic ductal adenocarcinoma (PDAC) is due to hypermethylation of Core 1 synthase specific molecular chaperone (COSMC) and enhanced the malignant properties of PDAC cells with an unknown mechanism. To explore the mechanism, we have genetically deleted COSMC in PDAC cells to express truncated O-glycans (SimpleCells, SC) which enhanced cell migration and invasion. Since epithelial-to-mesenchymal transition (EMT) play a vital role in metastasis, we have analysed the induction of EMT in SC cells. Expressions of the mesenchymal markers were significantly high in SC cells as compared to WT cells. Equally, we found reduced expressions of the epithelial markers in SC cells. Re-expression of COSMC in SC cells reversed the induction of EMT. In addition to this, we also observed an increased cancer stem cell population in SC cells. Furthermore, orthotopic implantation of T3M4 SC cells into athymic nude mice resulted in significantly larger tumours and reduced animal survival. Altogether, these results suggest that aberrant expression of truncated O-glycans in PDAC cells enhances the tumour aggressiveness through the induction of EMT and stemness properties.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787448 | PMC |
| http://dx.doi.org/10.1111/jcmm.14572 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Analyses of biosynthesis mutants reveal that the fifth and sixth sugars of the Porphyromonas gingivalis O-glycan are L-fucose and N-acetylgalactosamine respectively.
Gene
March 2025
Melbourne Dental School, Bio21 Institute, The University of Melbourne, Parkville, Victoria, Australia. Electronic address:
The oral pathogen, Porphyromonas gingivalis has a general O-glycosylation system which it utilises to modify hundreds of proteins localised outside of the cytoplasm. The O-glycan is a heptasaccharide that includes a putative L-fucose and N-acetylgalactosamine (GalNAc) as the 5th and 6th sugar residues respectively. The putative L-fucose is expected to be synthesized as GDP-L-fucose involving the enzymes Gmd (PGN_1078) and Fcl (PGN_1079), while GalNAc is putatively epimerised from GlcNAc by GalE (PGN_1614).
View Article and Find Full Text PDFSialyl-Tn glycan epitope as a target for pancreatic cancer therapies.
Front Oncol
September 2024
Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Porto, Portugal.
Pancreatic cancer (PC) is the sixth leading cause of cancer-related deaths worldwide, primarily due to late-stage diagnosis and limited treatment options. While novel biomarkers and immunotherapies are promising, further research into specific molecular targets is needed. Glycans, which are carbohydrate structures mainly found on cell surfaces, play crucial roles in health and disease.
View Article and Find Full Text PDFN-acetylgalactosaminyltransferase GALNT6 is a potential therapeutic target of clear cell renal cell carcinoma progression.
Cancer Sci
October 2024
Department of Colorectal Surgery, The First Affiliated Hospital of China Medical University, Shenyang, China.
High expression of truncated O-glycans Tn antigen predicts adverse clinical outcome in patients with clear cell renal cell carcinoma (ccRCC). To understand the biosynthetic underpinnings of Tn antigen changes in ccRCC, we focused on N-acetylgalactosaminyltransferases (GALNTs, also known as GalNAcTs) known to be involved in Tn antigen synthesis. Data from GSE15641 profile and local cohort showed that GALNT6 was significantly upregulated in ccRCC tissues.
View Article and Find Full Text PDFSubstrate O-glycosylation actively regulates extracellular proteolysis.
Protein Sci
August 2024
Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.
Extracellular proteolysis critically regulates cellular and tissue responses and is often dysregulated in human diseases. The crosstalk between proteolytic processing and other major post-translational modifications (PTMs) is emerging as an important regulatory mechanism to modulate protease activity and maintain cellular and tissue homeostasis. Here, we focus on matrix metalloproteinase (MMP)-mediated cleavages and N-acetylgalactosamine (GalNAc)-type of O-glycosylation, two major PTMs of proteins in the extracellular space.
View Article and Find Full Text PDFThe Cerebrospinal Fluid Free-Glycans Hex and HexNAcHexNeu5Ac as Potential Biomarkers of Alzheimer's Disease.
Biomolecules
April 2024
Institute of Diagnostic Laboratory Medicine, Clinical Chemistry, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, Germany.
Alzheimer's disease (AD) is the most common neurodegenerative disorder, affecting a growing number of elderly people. In order to improve the early and differential diagnosis of AD, better biomarkers are needed. Glycosylation is a protein post-translational modification that is modulated in the course of many diseases, including neurodegeneration.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!