The Essential Role of N-Glycosylation in Integrin αV and uPAR Interaction in Glioblastoma DOI

Gretel Magalí Ferreira,

Héctor Cuello,

Aylen Camila Nogueira

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 2, 2024

Abstract BACKGROUND Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults, characterized by poor patient survival rates. The glycoproteins Integrin αV (IαV), Urokinase-type plasminogen activator receptor (uPAR) are key contributors to malignancy GBM, although their interaction well-described, role of glycans this process has been scarcely evaluated. Better understanding could enhance our knowledge disease lead potential new therapeutics.METHODS We investigated between IαV uPAR human A172 LN229, low-grade glioma, SW1088, cell lines. Expression these proteins was confirmed via confocal microscopy co-immunoprecipitation. N-glycosylation evaluated using inhibitor Swainsonine (SW) glycosidase PNGase F. Glycoproteomic analysis mass spectrometry identified glycosylation sites differential structures on IαV. impact sialic acids specific glycan assessed Neuraminidase (NeuA) lectin binding assays.RESULTS expression uPAR, as well interaction, GBM cells but not glioma cells, even when overexpressed. SW treatments markedly reduced IαV/uPAR highlighting importance N-glycosylation. Mass showed six with complex hybrid N-glycans, while only oligomannose N-glycans were detected cells. NeuA treatment also underscoring acids. Lectin assays suggested β1–6 branched at crucial for interaction. Inhibition acid removal both decreased AKT phosphorylation, indicating a significant integrin/uPAR signaling.CONCLUSIONS Our results demonstrate first time critical N-glycosylation, particularly

Language: Английский

Emerging trends in post-translational modification: Shedding light on Glioblastoma multiforme DOI
Smita Kumari,

Rohan Gupta,

Rashmi K. Ambasta

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2023, Volume and Issue: 1878(6), P. 188999 - 188999

Published: Oct. 18, 2023

Language: Английский

Citations

7
Dissecting causal relationships between gut microbiota, blood metabolites, and glioblastoma multiforme: a two-sample Mendelian randomization study DOI Creative Commons

Xuan Chen,

Lihui Han,

Wenzhe Xu

et al.

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: July 3, 2024

Background Given the increasing interest in role of gut microbiota glioblastoma multiforme (GBM), our objective was to examine potential causal relationship between and GBM, as well mediating effects specific metabolites. Methods A bidirectional two-sample Mendelian randomization (MR) analysis conducted investigate associations 196 microbial taxa GBM. two-step MR technique used identify significant mediators this relationship. Subsequently, a mediation performed explore quantify metabolites on Results Five showed with Among them, family Victivallaceae [odds ratio (OR): 1.95; 95% confidence interval (CI): 1.21, 3.13; p = 0.005] genus Lactococcus (OR: 1.81; CI: 1.04, 3.15; 0.036) were positively correlated risk while phylum Cyanobacteria had protective effect against GBM 0.45; 0.22, 0.89; 0.021). The revealed that connections among Victivallaceae, Lactococcus, mediated by Methyl-4-hydroxybenzoate sulfate, phosphoethanolamine dehydroepiandrosterone sulfate. Each these accounted for 7.27, 7.98, 8.65%, respectively. Conclusion Our study provides evidence supporting association certain highlights central pathogenesis their interactions vital serum This paves way novel therapeutic interventions management.

Language: Английский

Citations

0
Histone Acetyl Transferase 1 Is Overexpressed in Poor Prognosis, High-grade Meningeal and Glial Brain Cancers: Immunohistochemical and Aptahistochemical Study DOI

Sandra Bargiela-Cuevas,

María Marin,

María Gabaldon-Ojeda

et al.

Journal of Histochemistry & Cytochemistry, Journal Year: 2024, Volume and Issue: 72(8-9), P. 585 - 599

Published: Aug. 24, 2024

Primary malignancies of the central nervous system account for 2% all cancers in adults and almost 15% children under 15 years age. The prognosis brain anaplastic glioblastomas remains extremely poor, with devastating survival expectative, new molecular markers therapeutic targets are essential. Epigenetic changes constitute an extensive field development diagnostic strategies. Histone acetyl transferase-1 (HAT1) has merged as a potential prognostic marker therapy target different malignancies. Data repository analysis showed HAT1 mRNA overexpression gliomas been described its alternative splicing glioblastomas. Using immunohistochemical aptahistochemical methods, we analyzed expression meningiomas, oligodendrogliomas, astroglial cancers. We observed that is associated most aggressive tumor types worse prognosis, well higher probability early relapse meningiomas. Its cytosolic localization correlates progression prognosis. Aptamers, synthetic oligonucleotides capable to bind inhibit wide variety targets, considered promising tools. Aptahistochemistry using aptamer apHAT610 offered superior results comparison antibody used, good example aptamers tools histopathology.

Language: Английский

Citations

0
The Essential Role of N-Glycosylation in Integrin αV and uPAR Interaction in Glioblastoma DOI

Gretel Magalí Ferreira,

Héctor Cuello,

Aylen Camila Nogueira

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 2, 2024

Abstract BACKGROUND Glioblastoma multiforme (GBM) is the most common and aggressive brain tumor in adults, characterized by poor patient survival rates. The glycoproteins Integrin αV (IαV), Urokinase-type plasminogen activator receptor (uPAR) are key contributors to malignancy GBM, although their interaction well-described, role of glycans this process has been scarcely evaluated. Better understanding could enhance our knowledge disease lead potential new therapeutics.METHODS We investigated between IαV uPAR human A172 LN229, low-grade glioma, SW1088, cell lines. Expression these proteins was confirmed via confocal microscopy co-immunoprecipitation. N-glycosylation evaluated using inhibitor Swainsonine (SW) glycosidase PNGase F. Glycoproteomic analysis mass spectrometry identified glycosylation sites differential structures on IαV. impact sialic acids specific glycan assessed Neuraminidase (NeuA) lectin binding assays.RESULTS expression uPAR, as well interaction, GBM cells but not glioma cells, even when overexpressed. SW treatments markedly reduced IαV/uPAR highlighting importance N-glycosylation. Mass showed six with complex hybrid N-glycans, while only oligomannose N-glycans were detected cells. NeuA treatment also underscoring acids. Lectin assays suggested β1–6 branched at crucial for interaction. Inhibition acid removal both decreased AKT phosphorylation, indicating a significant integrin/uPAR signaling.CONCLUSIONS Our results demonstrate first time critical N-glycosylation, particularly

Language: Английский

Citations

0