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Aberrant O-glycosylation modulates aggressiveness in neuroblastoma
- Source :
- Oncotarget
- Publication Year :
- 2018
-
Abstract
- Neuroblastoma (NB) is the most common pediatric malignancy diagnosed before the first birthday in which MYCN oncogene amplification is associated with poor prognosis. Although aberrant glycosylation is an important actor in cell biology, little is known about its role in pediatric cancers such as NB. In this work we characterized the glycophenotype and the enzyme expression involved in glycans biosynthesis in five established human NB cell lines and in patient-derived primary tumors with different MYCN status. Our results show a high expression of Lewis glycan family both in MYCN-amplified cell lines and patient samples. Additionally, we report that MYCN-amplified cells overexpressed Core 2-initiating glycosyltransferase C2GNT1 in association with specific ST3Gals and FUTs, and showed increased binding to E- and P- selectins. Silencing of C2GNT1 expression in NB cells diminished expression of Lewis glycans, decreased the E- and P-selectin binding, and reduced cell adhesion, migration and proliferation in vitro. Treatment of MYCN-non-amplified cells with Trichostatin A (TSA), an histone deacetylase inhibitor, increased the expression of Lewis glycans and the enzymes involved in their biosynthesis. Our results demonstrate that MYCN-amplified NB cells overexpress Lewis family glycans, which belong to the Core 2 O-glycans group. Their expression plays a key role in the malignant behaviour of the NB cells and it is modulated by epigenetic mechanisms.
- Subjects :
- 0301 basic medicine
Glycan
Glycosylation
medicine.drug_class
glycophenotype
03 medical and health sciences
chemistry.chemical_compound
neuroblastoma
0302 clinical medicine
Neuroblastoma
MYCN
medicine
Gene silencing
O-glycans
Cell adhesion
neoplasms
biology
Chemistry
Histone deacetylase inhibitor
histone acetylation
medicine.disease
030104 developmental biology
Trichostatin A
Oncology
Cell culture
030220 oncology & carcinogenesis
biology.protein
Cancer research
medicine.drug
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 9
- Issue :
- 75
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....9831e66decb160b5b8b0e111abb81779