Core fucosylation as well as their modified glycoproteins associated with diseases
Ontology highlight
ABSTRACT:
ORGANISM(S): 智人（人类）
SUBMITTER: Guo
PROVIDER: PXD048588 | JPOST Repository | Wed Jan 17 00:00:00 GMT 2024
REPOSITORIES: jPOST
Similar Datasets
Project description:Core fucosylation, the attachment of α1,6-fucose to the innermost GlcNAc residue of N-glycans, is a unique protein glycosylation in living organisms. It plays significant roles in diverse physiological and pathological processes, and its upregulation has been observed in many cancers. Core fucosylation has a strong relationship with tumor growth, inva-sion, metastasis, prognosis, and immune evasion. Yet, the details are still largely unknown due to the lack of an effec-tive analytical method. Here, a site-specific and reversible labeling strategy for rapid and sensitive probing core fucosyla-tion was developed. Taking the newly developed strategy, core-fucosylated proteins located on the cell-surface were selectively labeled and analyzed. The profile of cell-surface glycoproteins provides an in-depth understanding of the biological functions of core fucosylation.
2022-08-13 | PXD036051 | iProX
Project description:Dysregulated metabolism in glioblastoma (GBM), the deadliest brain tumor of adults, offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome and the glycoproteome of human subgroup-specific GBM stem cells (GSCs). Here we report that L-Fucose abundance and core fucosylation activation are more highly enhanced in mesenchymal (MES) than in proneural (PN) GSCs; this pattern is retained in subgroup-specific xenografts and, most significantly, retrieved in subgroup-affiliated human patients’ samples. Genetic and pharmacological inhibition of core fucosylation in MES GBM preclinical models results in significant reduction in tumor burden. LC/MS-based glycoproteomic screening indicates that most MES-restricted core fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion and integrin-mediated signaling. Notably, selective L-Fucose accumulation in MES GBMs is demonstrated by pre-clinical minimally-invasive positron emission tomography (PET), implying this metabolite as a potential subgroup-restricted biomarker. Overall, these findings indicate that L-Fucose pathway activation in MES GBM offers subgroup-specific, GSC-restricted dependencies to be exploited as diagnostic markers and actionable therapeutic targets.
2022-11-08 | GSE202200 | GEO
Project description:Overexpression of fucosyltransferase 8 (FUT8) is found in many cancers including liver, ovarian, thyroid, colorectal and non-small cell lung cancers. Unlike other FUTs which are functionally redundant, FUT8 is the only enzyme responsible for the alpha1,6-linked fucosylation (core fucosylation) by adding fucose to the innermost GlcNAc residue of an N-linked glycan. A growing body of evidence indicates that core fucosylation is important for regulating protein functions, such as EGFR, TGF beta receptor and integrins. To understand the downstream molecular events in response to the global alteration of core fucosylation during cancer progression, microarray analysis was employed to profile the changes in gene expression following FUT8 silencing. The genes significantly (2-fold, P<0.01) changed in CL1-5/shFUT8 cells were selected for functional annotations using a Gene Ontology database. The result revealed that many genes involved in cell adhesion, motility, growth, angiogenesis, and inflammation were under the control of core fucosylation.
2012-12-07 | GSE42405 | GEO
Project description:Overexpression of fucosyltransferase 8 (FUT8) is found in many cancers including liver, ovarian, thyroid, colorectal and non-small cell lung cancers. Unlike other FUTs which are functionally redundant, FUT8 is the only enzyme responsible for the alpha1,6-linked fucosylation (core fucosylation) by adding fucose to the innermost GlcNAc residue of an N-linked glycan. A growing body of evidence indicates that core fucosylation is important for regulating protein functions, such as EGFR, TGF beta receptor and integrins. To understand the downstream molecular events in response to the global alteration of core fucosylation during cancer progression, microarray analysis was employed to profile the changes in gene expression following FUT8 silencing. The genes significantly (2-fold, P<0.01) changed in CL1-5/shFUT8 cells were selected for functional annotations using a Gene Ontology database. The result revealed that many genes involved in cell adhesion, motility, growth, angiogenesis, and inflammation were under the control of core fucosylation. In this experiment, the gene expression profile of two stable FUT8 knockdown clones of CL1-5 cells, CL1-5/shFUT8-1 and CL1-5/shFUT8-2, were compare with CL1-5/Control cells. A total of eight samples were analyzed, including four CL1-5/Control vs. CL1-5/shFUT8-1 and four CL1-5/Control vs. C1-5/shFUT8-2. The biological replicates for each cell lines were four.
2012-12-07 | E-GEOD-42405 | biostudies-arrayexpress
Project description:In this study, we provide a simple and straightforward method to distinguish core-fucosylated glycans from antenna-fucosylated glycans by systematically evaluating the extent of fucose migration based on the feature Y ions by using Fut8 knockout (Fut8−/−) mouse brain under HCD energy of 20%. The method was further evaluated by multiple different approaches including validation by standard glycopeptides, evaluation in silico, comparison under the lower energy (15%), and applied to analyze core-fucosylated glycans in wide-type (Fut8+/+) mouse brain.
2022-11-14 | PXD035158 | Pride
Project description:<p>Dysregulated metabolism in glioblastoma (GBM), the deadliest brain tumor of adults, offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome and the glycoproteome of human subgroup-specific GBM stem cells (GSCs).</p><p>Here we report that L-Fucose abundance and core fucosylation activation are more highly enhanced in mesenchymal (MES) than in proneural (PN) GSCs; this pattern is retained in subgroup-specific xenografts and, most significantly, retrieved in subgroup-affiliated human patients’ samples. Genetic and pharmacological inhibition of core fucosylation in MES GBM preclinical models results in significant reduction in tumor burden. LC/MS-based glycoproteomic screening indicates that most MES-restricted core fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion and integrin-mediated signaling. Notably, selective L-Fucose accumulation in MES GBMs is demonstrated by pre-clinical minimally-invasive positron emission tomography (PET), implying this metabolite as a potential subgroup-restricted biomarker.</p><p>Overall, these findings indicate that L-Fucose pathway activation in MES GBM offers subgroup-specific, GSC-restricted dependencies to be exploited as diagnostic markers and actionable therapeutic targets.</p><p><br></p><p><strong>Xenograft assays</strong> are reported in the current study <strong>MTBLS730</strong></p><p><strong>Stem cell and cell line assays</strong> are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4708' rel='noopener noreferrer' target='_blank'><strong>MTBLS4708</strong></a></p>
2022-11-08 | MTBLS730 | MetaboLights
Project description:<p>Dysregulated metabolism in glioblastoma (GBM), the deadliest brain tumor of adults, offers an opportunity to deploy metabolic interventions as precise therapeutic strategies. To identify the molecular drivers and the modalities by which different molecular subgroups of GBM exploit metabolic rewiring to sustain tumor progression, we interrogated the transcriptome, the metabolome and the glycoproteome of human subgroup-specific GBM stem cells (GSCs).</p><p>Here we report that L-Fucose abundance and core fucosylation activation are more highly enhanced in mesenchymal (MES) than in proneural (PN) GSCs; this pattern is retained in subgroup-specific xenografts and, most significantly, retrieved in subgroup-affiliated human patients’ samples. Genetic and pharmacological inhibition of core fucosylation in MES GBM preclinical models results in significant reduction in tumor burden. LC/MS-based glycoproteomic screening indicates that most MES-restricted core fucosylated proteins are involved in therapeutically relevant GBM pathological processes, such as extracellular matrix interaction, cell adhesion and integrin-mediated signaling. Notably, selective L-Fucose accumulation in MES GBMs is demonstrated by pre-clinical minimally-invasive positron emission tomography (PET), implying this metabolite as a potential subgroup-restricted biomarker.</p><p>Overall, these findings indicate that L-Fucose pathway activation in MES GBM offers subgroup-specific, GSC-restricted dependencies to be exploited as diagnostic markers and actionable therapeutic targets.</p><p><br></p><p><strong>Stem cell and cell line assays</strong> are reported in the current study <strong>MTBLS4708</strong></p><p><strong>Xenograft assays</strong> are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS730' rel='noopener noreferrer' target='_blank'><strong>MTBLS730</strong></a></p>
2022-11-08 | MTBLS4708 | MetaboLights
Project description:Glycoproteomic screening indicates that core fucosylation activation is more highly enhancedin mesenchymal (MES) than in proneural (PN) glioblastoma cancer stem cells (GSCs) and this pattern is retained in subgroup-specific xenograftsand human patients’ samples. Most MES-restricted core fucosylated proteins are involved in therapeutically relevant pathological processes, such as extracellular matrix interaction and tumor invasion.
2022-11-09 | PXD033408 | Pride
Project description:Natural Killer (NK) cell development and effector function requires context-dependent signalling via numerous receptors including the IL-15 receptor. The modulation of receptor signalling can be regulated by the post-translational modifications affecting receptor turnover and trafficking. Core fucosylation is one such modification known to impact receptor expression and is uniquely mediated by fucosyltransferase 8 (FUT8). To investigate core fucosylation in NK cell biology, we generated mice lacking FUT8 in NK cells (Fut8fl/flNcr1cre/+). Loss of core fucose resulted in pronounced NK lymphopenia in Fut8fl/flNcr1cre/+ mice associated with a reduction in IL-15 receptor expression and loss of in vivo proliferation. Inhibition of intrinsic apoptosis pathways could not overcome compromised IL-15 receptor signalling to rescue FUT8-null NK cell development delineating the contribution of proliferation to NK cell homeostasis. Surprisingly, loss of core fucose enhanced NK cell expansion following viral infection and this was associated with upregulation of IL-2Rα following pro-inflammatory cytokine exposure and enhanced IL-2-mediated proliferation. Lastly, loss of FUT8 activity impaired TGFBR2 expression and immunosuppressive effects of TGF-β on NK cells. Taken together, we have identified fucosyltransferase 8 as a key modulator of NK cell development and function by regulating IL-15 receptor responsiveness.
2024-01-01 | GSE243190 | GEO
Project description:Purpose: Core 3 derived glycans, a major type of O-glycan expressed by normal epithelial cells of the gastrointestinal tract, are downregulated during malignancy, because of loss of expression of functional β3-N-acetylglucosaminyltransferase-6 (core 3 synthase). We investigated the expression of core 3 synthase in normal pancreas and pancreatic cancer and evaluated the biological effects of re-expressing core 3 synthase in pancreatic cancer cells that had lost expression. Experimental Design: We determined that pancreatic tumors and tumor cell lines have lost expression of core 3 synthase. We therefore re-expressed in human pancreatic cancer cells (Capan-2 and FG) to investigate the contribution of core 3 glycans to malignant progression. Results: Pancreatic cancer cells expressing core 3 synthase showed reduced in vitro cell proliferation, migration and invasion compared with vector control cells. Expression of core 3 O-glycans induced altered expression of β1 integrin, decreased activation of focal adhesion kinase, led to the down regulation of expression of several genes including REG1α and FGFR3, and altered lamellipodia formation. The addition of a GlcNAc residue by core 3 synthase leads to the extension of the tumor associated Tn structure on MUC1. Orthotopic injection of FG cells expressing core 3 synthase into the pancreas of nude mice produced significantly smaller tumors and decreased metastasis to the surrounding tissues compared to vector control FG cells. Conclusions: These findings indicate that expression of core 3 derived O-glycans in pancreatic cancer cells suppresses tumor growth and metastasis through modulation of glycosylation of mucins and other cell surface and extracellular matrix proteins. Two-condition experiment, Core 3 synthase stable expression (C3) vs. vector control (PLVX) cells. Biological replicates: 3 Core 3 synthase stable expression, 3 vector control, independently grown and harvested. One replicate per array.
2012-11-21 | E-GEOD-42417 | biostudies-arrayexpress