Dataset Information

A “One-step” Strategy for the Global Characterization of Core-Fucosylated Glycoproteome

ABSTRACT: Core fucosylation, a special type of N-linked glycosylation, is important in tumor proliferation, invasion, metastatic potential, and therapy resistance. However, the core-fucosylated glycoproteome has not been extensively profiled due to the low abundance and poor ionization efficiency of glycosylated peptides. Here, a “one-step” strategy has been described for protein core-fucosylation characterization in biological samples. Core-fucosylated peptides can be selectively labeled with a glycosyl-ated probe, which is linked with a temperature-sensitive poly(N-isopropylacrylamide) polymer (PNIPAM), by mutant endo-glycosidase (EndoF3-D165A). The labeled probe can be further removed by wild-type endoglycosidase (EndoF3) in a trace-less manner for mass spectrometry (MS) analysis. The feasibility and effectiveness of the “one-step” strategy are evaluated in the bovine serum albumin (BSA) spiked with standard core-fucosylated peptides, H1299, and Jurkat cell lines. The “one-step” strategy is then employed to characterize core-fucosylated sites in human lung adenocarcinoma, resulting in the identifica-tion of 2494 core-fucosylated sites distributed on 1176 glycoproteins. Further data analysis reveals that 196 core-fucosylated sites are significantly upregulated in tumors, which may serve as potential drug development targets or diagnos-tic biomarkers. Together, this “one-step” strategy has great potential for use in global and in-depth analysis of core-fucosylated glycoproteome to promote its mechanism research.

ORGANISM(S): Homo Sapiens

SUBMITTER: Hu Zhou

PROVIDER: PXD051139 | iProX | Tue Apr 02 00:00:00 BST 2024

REPOSITORIES: iProX

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A "One-Step" Strategy for the Global Characterization of Core-Fucosylated Glycoproteome.

Wang Yuqiu Y Yuan Rui R Liang Bo B Zhang Jing J Wen Qin Q Chen Hongxu H Tian Yinping Y Wen Liuqing L Zhou Hu H

JACS Au 20240501 5

Core fucosylation, a special type of N-linked glycosylation, is important in tumor proliferation, invasion, metastatic potential, and therapy resistance. However, the core-fucosylated glycoproteome has not been extensively profiled due to the low abundance and poor ionization efficiency of glycosylated peptides. Here, a "one-step" strategy has been described for protein core-fucosylation characterization in biological samples. Core-fucosylated peptides can be selectively labeled with a gl ...[more]

PMID: 38818065

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Project description:Glioblastoma (GBM) is a common and deadly form of brain tumor in adults. Dysregulated metabolism in GBM 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 sphere-forming cells (GSC). L-fucose abundance and core fucosylation activation were elevated in mesenchymal (MES) compared with proneural GSCs; this pattern was retained in subgroup-specific xenografts and in subgroup-affiliated human patient samples. Genetic and pharmacological inhibition of core fucosylation significantly reduced tumor growth in MES GBM preclinical models. Liquid chromatography-mass spectrometry (LC-MS)-based glycoproteomic screening indicated 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. Selective L-fucose accumulation in MES GBMs was observed using preclinical minimally invasive PET, implicating this metabolite as a potential subgroup-restricted biomarker.Overall, these findings indicate that L-fucose pathway activation in MES GBM is a subgroup-specific dependency that could provide diagnostic markers and actionable therapeutic targets.<h4>SIGNIFICANCE: Metabolic characterization of subgroup-specific glioblastoma (GBM) sphere-forming cells identifies the L-fucose pathway as a vulnerability restricted to mesenchymal GBM, disclosing a potential precision medicine strategy for targeting cancer metabolism.</h4> Xenograft assays are reported in the current study MTBLS730.Stem cell and cell line assays are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4708' rel='noopener noreferrer' target='_blank'>MTBLS4708</a>.

Project description:Glioblastoma (GBM) is a common and deadly form of brain tumor in adults. Dysregulated metabolism in GBM 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 sphere-forming cells (GSC). L-fucose abundance and core fucosylation activation were elevated in mesenchymal (MES) compared with proneural GSCs; this pattern was retained in subgroup-specific xenografts and in subgroup-affiliated human patient samples. Genetic and pharmacological inhibition of core fucosylation significantly reduced tumor growth in MES GBM preclinical models. Liquid chromatography-mass spectrometry (LC-MS)-based glycoproteomic screening indicated 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. Selective L-fucose accumulation in MES GBMs was observed using preclinical minimally invasive PET, implicating this metabolite as a potential subgroup-restricted biomarker.Overall, these findings indicate that L-fucose pathway activation in MES GBM is a subgroup-specific dependency that could provide diagnostic markers and actionable therapeutic targets.<h4>SIGNIFICANCE: Metabolic characterization of subgroup-specific glioblastoma (GBM) sphere-forming cells identifies the L-fucose pathway as a vulnerability restricted to mesenchymal GBM, disclosing a potential precision medicine strategy for targeting cancer metabolism.</h4> Stem cell and cell line assays are reported in the current study <a href='https://www.ebi.ac.uk/metabolights/MTBLS4708' rel='noopener noreferrer' target='_blank'>MTBLS4708</a>.Xenograft assays are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS730' rel='noopener noreferrer' target='_blank'>MTBLS730</a>.

Dataset Information

A “One-step” Strategy for the Global Characterization of Core-Fucosylated Glycoproteome

Publications

A "One-Step" Strategy for the Global Characterization of Core-Fucosylated Glycoproteome.

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