To define the role of glycosylation in the interaction and metastatic behaviour of tumor cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Steven Head
PROVIDER: E-GEOD-31936 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The aim of our study is to define the role of glycosylation in the interaction of pancreatic tumor cells with dendritic cells and/or in the metastatic behaviour of the tumor cells.
2011-09-06 | GSE31936 | GEO
Project description:Aberrant glycosylation involves multifaceted pathological and pathophysiological changes in pancreatic ductal adenocarcinoma (PDAC), including but not limited to conferring tumor cells the ability to resist cell death. Ferroptosis driven by lethal lipid peroxidation provides a targetable vulnerability to PDAC. However, the crosstalk between glycosylation and ferroptosis remains unclear. Here, we identified 4F2hc, a subunit of the glutamate-cystine antiporter system Xc–, its N-glycosylation is involved in PDAC ferroptosis by N- and O-linked glycoproteomics. Knockdown of SLC3A2 (gene name of 4F2hc) or blocking the N-glycosylation of 4F2hc potentiates ferroptosis sensitization of PDAC cells by impairing the activity of system Xc– manifested by a marked decrease in intracellular glutathione. To identify which glycosyltransferases are critical for glycosylation initiation during ferroptosis execution. We collected 207 glycosyltransferase genes (GTGs) and performed parallel RNA-seq to reveal that the glycosyltransferase B3GNT3 catalyzes the glycosylation of 4F2hc, which stabilizes the 4F2hc protein as well as its interaction with xCT. Additionally, upon the combination with a ferroptosis inducer, treatment with the classical N-glycosylation inhibitor tunicamycin (TM) markedly triggered the overactivation of lipid peroxidation and enhanced the sensitivity of PDAC cells to ferroptosis. Notably, we confirmed that genetic perturbation of SLC3A2 or combination treatment with TM markedly increased ferroptosis sensitivity in the orthotopic PDAC model. Clinically, high expression of 4F2hc and B3GNT3 contributes to the progression and poor survival of PDAC patients. Collectively, our findings reveal a previously unappreciated function of N-glycosylation of 4F2hc in ferroptosis and suggest that targeting glycosylated 4F2hc can induce susceptibility to ferroptosis in PDAC.
2023-07-12 | GSE207741 | GEO
Project description:Apo2L/TRAIL stimulates cancer-cell death through the proapoptotic receptors DR4 and DR5, but the determinants of tumor susceptibility to this ligand are not fully defined. mRNA expression of the peptidyl O-glycosyl transferase GALNT14 correlated with Apo2L/TRAIL sensitivity in pancreatic carcinoma, non-small cell lung carcinoma and melanoma cell lines (P < 0.00009; n=83), and up to 30% of samples from various human malignancies displayed GALNT14 overexpression. RNA interference of GALNT14 reduced cellular Apo2L/TRAIL sensitivity, whereas overexpression increased responsiveness. Biochemical analysis of DR5 identified several ectodomain O-GalNAc-Gal-Sialic acid structures. Sequence comparison predicted conserved extracellular DR4 and DR5 O-glycosylation sites; progressive mutation of the DR5 sites attenuated apoptosis signaling. O-glycosylation promoted ligand-stimulated clustering of DR4 and DR5, which mediated recruitment and activation of the apoptosis-initiating protease caspase-8. These results uncover a novel link between death receptor O-glycosylation and apoptosis signaling, providing potential predictive biomarkers for Apo2L/TRAIL-based cancer therapy. Keywords: cell type comparison
2007-08-31 | GSE8332 | GEO
Project description:KIAA1324 is a transmembrane protein largely reported as a tumor suppressor and favorable prognosis marker in various cancers, including gastric cancer. In this study, we report the role of N-linked glycosylation in KIAA1324 as a functional post-translational modification (PTM). Loss of N-linked glycosylation eliminated the potential of KIAA1324 to suppress cancer cell proliferation and migration. Furthermore, we demonstrated that KIAA1324 undergoes fucosylation, a modification of the N-glycan mediated by fucosyltransferase, and inhibition of fucosylation also significantly suppressed KIAA1324-induced cell growth inhibition and apoptosis of gastric cancer cells. In addition, KIAA1324-mediated apoptosis and tumor regression were inhibited by the loss of N-linked glycosylation. RNA sequencing (RNAseq) analysis revealed that genes most relevant to the apoptosis and cell cycle arrest pathways were modulated by KIAA1324 with the N-linked glycosylation, and Gene Regulatory Network (GRN) analysis suggested novel targets of KIAA1324 for anti-tumor effects in transcription level. The N-linked glycosylation blockade decreased protein stability through rapid proteasomal degradation. The non-glycosylated mutant also showed altered localization and lost apoptotic activity that inhibits the interaction between GRP78 and caspase 7. These data demonstrate that N-linked glycosylation of KIAA1324 is essential for the suppressive role of KIAA1324 protein in gastric cancer progression and indicates that KIAA1324 may have anti-tumor effects by targeting cancer-related genes with N-linked glycosylation. In conclusion, our study suggests the PTM of KIAA1324 including N-linked glycosylation and fucosylation is a necessary factor to consider for cancer prognosis and therapy improvement.
2023-08-07 | GSE239904 | GEO
Project description:These research areas concentrate on stress induced proteases in recombinant Escherichia coli, glycosylation heterogeneity due to bioprocess conditions produced in mammalian cells, and metabolic engineering of E. coli. The hypothesis of this project is that recombinant protein glycosylation is inefficient under normal bioreactor conditions since the additional glycosylation reactions necessary for the recombinant protein exceed the metabolic capacity of the cells. Normal bioreactor conditions have been optimized for cell growth, and sometimes for protein productivity. Only recently has it been accepted that optimal glycosylation may not occur under optimal growth or protein productivity conditions. Specific Aim: Determine the relationship between bioreactor conditions and glycosylation gene expression in NS0 cells.
2011-04-29 | GSE28920 | GEO
Project description:Apo2L/TRAIL stimulates cancer-cell death through the proapoptotic receptors DR4 and DR5, but the determinants of tumor susceptibility to this ligand are not fully defined. mRNA expression of the peptidyl O-glycosyl transferase GALNT14 correlated with Apo2L/TRAIL sensitivity in pancreatic carcinoma, non-small cell lung carcinoma and melanoma cell lines (P < 0.00009; n=83), and up to 30% of samples from various human malignancies displayed GALNT14 overexpression. RNA interference of GALNT14 reduced cellular Apo2L/TRAIL sensitivity, whereas overexpression increased responsiveness. Biochemical analysis of DR5 identified several ectodomain O-GalNAc-Gal-Sialic acid structures. Sequence comparison predicted conserved extracellular DR4 and DR5 O-glycosylation sites; progressive mutation of the DR5 sites attenuated apoptosis signaling. O-glycosylation promoted ligand-stimulated clustering of DR4 and DR5, which mediated recruitment and activation of the apoptosis-initiating protease caspase-8. These results uncover a novel link between death receptor O-glycosylation and apoptosis signaling, providing potential predictive biomarkers for Apo2L/TRAIL-based cancer therapy. Experiment Overall Design: Gene expression for untreated cell lines analyzed. Some cell lines have one replicate profile, some two (Samples with 2 CEL files). Normalized data for replicates was averaged. Analysis involved a regularized t-test to identify genes with expression differences between Apo2L sensitive and resistant lines.
2008-06-16 | E-GEOD-8332 | biostudies-arrayexpress
Project description:These research areas concentrate on stress induced proteases in recombinant Escherichia coli, glycosylation heterogeneity due to bioprocess conditions produced in mammalian cells, and metabolic engineering of E. coli. The hypothesis of this project is that recombinant protein glycosylation is inefficient under normal bioreactor conditions since the additional glycosylation reactions necessary for the recombinant protein exceed the metabolic capacity of the cells. Normal bioreactor conditions have been optimized for cell growth, and sometimes for protein productivity. Only recently has it been accepted that optimal glycosylation may not occur under optimal growth or protein productivity conditions. Specific Aim: Determine the relationship between bioreactor conditions and glycosylation gene expression in NS0 cells. EXPERIMENT: Mouse NS0 myeloma cells were grown in culture, stressed with 5 mM NaCl, 10 mM proline plus 5 mM ammonia, or 5 mM ammonia, along with an unstressed control group. The growth of the cultures were followed until the late exponential phase (90 hours), at which time two 50 mLs of cells were harvested and RNA extracted. Samples were prepared in triplicate, for a total of 12 samples. The RNA was amplified and labeled by Microarray Core (E) and hybridized to the GLYCOv3 microarrays.
2011-04-29 | E-GEOD-28920 | biostudies-arrayexpress
Project description:Dr. Jameson's research focus is on development and regulation of lymphocytes, especially T cells. Recent work has suggested that differential glycosylation effects the sensitivity of the T cell receptors and its coreceptors, suggesting that regulation of glycosylation may be a critical element in controlling T cell development, survival and functional activity.
2010-12-11 | GSE26012 | GEO
Project description:Dr. Clausen's laboratory is interested in the structure, biosynthesis and genetic regulation of glycoconjugates, with a major focus on mucins. This laboratory is studying the glycosylation and secretion process of mucins and biological functions involving mucins. This lab is also interested in receptor modulation mediated by glycosylation or through glycosphingolipids. RNA samples from two human pancreatic cell lines. The relevance of the variable expression levels of isoforms belonging to the polypeptide GalNAc-transferase gene-family is still a puzzle to us. The polypeptide GalNAc-transferase gene family is estimated to contain 24 gene-members all participating in the initiation of mucin-type O-glycosylation. It has become apparent that each of these individual isoforms have different tissue distribution profiles and kinetic capabilities. Mucin-type O-glycosylation is thus controlled, and dependent upon the repetoir of expressed GalNAc-transferases in any given organ and cell type at any given time. We have been trying to contribute to the understanding of the ordered process controlling mucin-type O-glycosylation in both normal and malignant models, and are currently investigating a pancreatic cell line model in the lab. The pancreatic tumor cell line ASPC-1 has been found to possess low metastatic potential in mouse models, in contrast to the pancreatic tumor cell line Suit-T2 possessing high metastatic potential. Immunohistochemical analysis of both cell lines, ASPC-1 and Suit-T2, using our monoclonal antibodies to 7 isoforms has revealed great differences in the expression profile of these 7 isoforms in theses two cell lines, and for instance GalNAc-T3 has been found to be highly expressed in Suit-T2 but completely lacking in ASPC-1. Two cell lines: ASPC-1 and Suit-T2 are analyzed with 3 independent replicate prepared for each cell line.
2010-12-11 | E-GEOD-26011 | biostudies-arrayexpress
Project description:The biological consequences of various IL-6 glycoforms are unknown. To uncover the function of N-glycosylation of IL-6 in lung cancer, we compare the gene expression profiles in NSCLC cells induced by conditioned medium containing IL-6 with complete N-glycosylation (NG-IL6) or defective N-glycosylation (deNG-IL6).
2024-07-16 | GSE269782 | GEO