Proteomics

Dataset Information

0

O-GlcNAcase activity is necessary for the molecular signature of the Glioblastoma secretome


ABSTRACT: Glioblastoma (GBM) is a grade IV glioma highly aggressive and refractory to the therapeutic approaches currently in use nowadays. Although sugar metabolism through the hexosamine biosynthetic pathway (HBP) plays a key role in tumor aggressiveness and progression in different types of cancer, whether the HBP might be a targetable strategy for GBM is still lacking experimental evidence. Here we show that the HBP enzyme O-GlcNAcase (OGA) plays a critical role in GBM secretome signature. Using a label-free quantitative proteomics methodology, we identified 51 proteins in the GBM secretome whose abundance was significantly altered. Among these proteins, we observed that proteins related to proteasome activity and autophagy were consistently down-regulated in GBM cells upon OGA activity inhibition (iOGA). While the proteins IGFBP3 and HSPA5 were down regulated in iOGA GBM cells, the protein SQSTM1/p62 was a only identified in iOGA GBM cells. These in silico findings were in line with experimental evidence showing a decrease in autophagy in iOGA cells followed by a decrease in radio-resistance. Taken together our findings consistently bridge the protein profile in the secretome with functional evidence of autophagy regulation in GBM by the OGA activity. We propose that the assessment of tumor status from the main proteins present in its secretome may contribute to the advancement of diagnostic, prognostic and even therapeutic tools to approach this relevant malignancy.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Glioblastoma

SUBMITTER: Joseph Evaristo  

LAB HEAD: Fábio César Sousa Nogueira

PROVIDER: PXD019496 | Pride | 2021-09-09

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
Katia_Analise_LCMS_2019_PD_Result.pdResult Other
QE-003463_Katia_ELU_A1-A.raw Raw
QE-003464_Katia_ELU_A1-B.raw Raw
QE-003465_Katia_ELU_A1-C.raw Raw
QE-003467_Katia_ELU_A2-A.raw Raw
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Publications

O-GlcNAcylation protein disruption by Thiamet G promotes changes on the GBM U87-MG cells secretome molecular signature.

Oliveira-Nunes Maria Cecilia MC   Julião Glaucia G   Menezes Aline A   Mariath Fernanda F   Hanover John A JA   Evaristo Joseph Albert Medeiros JAM   Nogueira Fábio César Sousa FCS   Dias Wagner Barbosa WB   de Abreu Pereira Denise D   Carneiro Katia K  

Clinical proteomics 20210426 1


Glioblastoma (GBM) is a grade IV glioma highly aggressive and refractory to the therapeutic approaches currently in use. O-GlcNAcylation plays a key role for tumor aggressiveness and progression in different types of cancer; however, experimental evidence of its involvement in GBM are still lacking. Here, we show that O-GlcNAcylation plays a critical role in maintaining the composition of the GBM secretome, whereas inhibition of OGA activity disrupts the intercellular signaling via microvesicles  ...[more]

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