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Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma

Cuello, Hector A. ; Ferreira, Gretel M. ; Gulino, Cynthia A. ; Toledo, Alejandro Gomez LU ; Segatori, Valeria I. and Gabri, Mariano R. (2021) In Oncotarget 11(35). p.4822-4835
Abstract

Gliomas are the most common intracranial primary tumors, for which very few therapeutic options are available. The most malignant subtype is the glioblastoma, a disease associated with a 5-year survival rate lower than 5%. Given that research in glycobiology continues highlighting the role of glycans in tumor cell biology, it offers an interesting niche for the search of new therapeutic targets. In this study, we characterized aberrant glycosylation and its impact on cell biology over a broad panel of high- and low-grade glioma cell lines. Results show high expression of terminal Lewis glycans, mainly SLex, and overexpression of sialyl- and fucosyltransferases involved in their biosynthesis in high-grade glioma cell lines.... (More)

Gliomas are the most common intracranial primary tumors, for which very few therapeutic options are available. The most malignant subtype is the glioblastoma, a disease associated with a 5-year survival rate lower than 5%. Given that research in glycobiology continues highlighting the role of glycans in tumor cell biology, it offers an interesting niche for the search of new therapeutic targets. In this study, we characterized aberrant glycosylation and its impact on cell biology over a broad panel of high- and low-grade glioma cell lines. Results show high expression of terminal Lewis glycans, mainly SLex, and overexpression of sialyl- and fucosyltransferases involved in their biosynthesis in high-grade glioma cell lines. Moreover, we report an association of complex multi-antennary N-glycans presenting β1,6-GlcNAc branches with the high-grade glioma cells, which also overexpressed the gene responsible for these assemblies, MGAT5. In addition, downmodulation of N-glycosylation by treatment with the inhibitors Tunicamycin/Swainsonine or MGAT5 silencing decreased SLex expression, adhesion and migration in high-grade glioma cells. In contrast, no significant changes in these cell capacities were observed in low-grade glioma after treatment with the N-glycosylation inhibitors. Furthermore, inhibition of histone deacetylases by Trichostatin A provoked an increase in the expression of SLex and its biosynthetic related glycosyltransferases in low-grade glioma cells. Our results describe that aggressive glioma cells show high expression of Lewis glycans anchored to complex multi-antennary N-glycans. This glycophenotype plays a key role in malignant cell behavior and is regulated by histone acetylation dependent mechanisms.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Glioblastoma, Glioma, Histone acetylation, Lewis glycans, N-glycans
in
Oncotarget
volume
11
issue
35
pages
14 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85099906066
ISSN
1949-2553
DOI
10.18632/ONCOTARGET.27850
language
English
LU publication?
yes
id
498506f1-717b-4069-a10b-8aeda4f7770d
date added to LUP
2021-02-08 11:35:55
date last changed
2021-02-08 11:35:55
@article{498506f1-717b-4069-a10b-8aeda4f7770d,
  abstract     = {<p>Gliomas are the most common intracranial primary tumors, for which very few therapeutic options are available. The most malignant subtype is the glioblastoma, a disease associated with a 5-year survival rate lower than 5%. Given that research in glycobiology continues highlighting the role of glycans in tumor cell biology, it offers an interesting niche for the search of new therapeutic targets. In this study, we characterized aberrant glycosylation and its impact on cell biology over a broad panel of high- and low-grade glioma cell lines. Results show high expression of terminal Lewis glycans, mainly SLe<sup>x</sup>, and overexpression of sialyl- and fucosyltransferases involved in their biosynthesis in high-grade glioma cell lines. Moreover, we report an association of complex multi-antennary N-glycans presenting β1,6-GlcNAc branches with the high-grade glioma cells, which also overexpressed the gene responsible for these assemblies, MGAT5. In addition, downmodulation of N-glycosylation by treatment with the inhibitors Tunicamycin/Swainsonine or MGAT5 silencing decreased SLe<sup>x</sup> expression, adhesion and migration in high-grade glioma cells. In contrast, no significant changes in these cell capacities were observed in low-grade glioma after treatment with the N-glycosylation inhibitors. Furthermore, inhibition of histone deacetylases by Trichostatin A provoked an increase in the expression of SLex and its biosynthetic related glycosyltransferases in low-grade glioma cells. Our results describe that aggressive glioma cells show high expression of Lewis glycans anchored to complex multi-antennary N-glycans. This glycophenotype plays a key role in malignant cell behavior and is regulated by histone acetylation dependent mechanisms.</p>},
  author       = {Cuello, Hector A. and Ferreira, Gretel M. and Gulino, Cynthia A. and Toledo, Alejandro Gomez and Segatori, Valeria I. and Gabri, Mariano R.},
  issn         = {1949-2553},
  language     = {eng},
  number       = {35},
  pages        = {4822--4835},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Terminally sialylated and fucosylated complex N-glycans are involved in the malignant behavior of high-grade glioma},
  url          = {http://dx.doi.org/10.18632/ONCOTARGET.27850},
  doi          = {10.18632/ONCOTARGET.27850},
  volume       = {11},
  year         = {2021},
}