Dataset Information

Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cells migration

ABSTRACT: Glioblastoma (GBM) is the most aggressive primary brain tumor characterized by infiltrative migration of malignant glioma cells into the surrounding brain parenchyma. In this study, our analysis of GBM patient cohorts displayed significant higher expression of Glycosyltransferase 8 domain containing 1 (GLT8D1) compared to normal brain tissue and could be associated with impaired patient survival. Increased in vitro expression of GLT8D1 significantly enhanced migration of two different sphere-forming GBM cell lines. By in silico analysis we predicted the 3D-structure as well as the active site residues of GLT8D1. The introduction of point mutations in the predicted active site reduced its glycosyltransferase activity in vitro and consequently impaired GBM tumor cell migration. Examination of GLT8D1 interaction partners by LC-MS/MS implied proteins associated with cytoskeleton and intracellular transport as potential substrates. In conclusion, we demonstrated that the enzymatic activity of glycosyltransferase GLT8D1 promotes GBM cell migration.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Gunnar Dittmar

LAB HEAD: Gunnar Dittmar

PROVIDER: PXD027854 | Pride | 2022-04-04

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	QHF_00005477_MQQC_HS_CJ_ctrl1.raw	Raw
	QHF_00005478_MQQC_HS_CJ_ctrl2.raw	Raw
	QHF_00005479_MQQC_HS_CJ_ctrl3.raw	Raw
	QHF_00005480_MQQC_HS_CJ_HA1-1.raw	Raw
	QHF_00005481_MQQC_HS_CJ_HA1-2.raw	Raw

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Publications

Enzymatic activity of glycosyltransferase GLT8D1 promotes human glioblastoma cell migration.

Ilina Elena I EI Cialini Camille C Gerloff Dietlind L DL Duarte Garcia-Escudero Maitane M Jeanty Céline C Thézénas Marie-Laëtitia ML Lesur Antoine A Puard Vincent V Bernardin François F Moter Alina A Schuster Anne A Dieterle Monika M Golebiewska Anna A Gérardy Jean-Jacques JJ Dittmar Gunnar G Niclou Simone P SP Müller Tanja T Mittelbronn Michel M

iScience 20220202 2

Glioblastoma (GBM) is the most aggressive primary brain tumor characterized by infiltrative growth of malignant glioma cells into the surrounding brain parenchyma. In this study, our analysis of GBM patient cohorts revealed a significantly higher expression of Glycosyltransferase 8 domain containing 1 (GLT8D1) compared to normal brain tissue and could be associated with impaired patient survival. Increased in vitro expression of GLT8D1 significantly enhanced mi ...[more]

PMID: 35198895

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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> 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>.