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Int. J. Mol. Sci. 2017, 18(11), 2262; https://doi.org/10.3390/ijms18112262

Gastric Cancer Cell Glycosylation as a Modulator of the ErbB2 Oncogenic Receptor

1
Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
2
Institute of Molecular Pathology and Immunology, University of Porto, 4200-135 Porto, Portugal
3
Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal
4
Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal
*
Authors to whom correspondence should be addressed.
Received: 28 September 2017 / Revised: 20 October 2017 / Accepted: 25 October 2017 / Published: 28 October 2017
(This article belongs to the Special Issue Kinase Signal Transduction 2017)
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Abstract

Aberrant expression and hyperactivation of the human epidermal growth factor receptor 2 (ErbB2) constitute crucial molecular events underpinning gastric neoplastic transformation. Despite ErbB2 extracellular domain being a well-known target for glycosylation, its glycosylation profile and the molecular mechanisms through which it actively tunes tumorigenesis in gastric cancer (GC) cells remain elusive. We aimed at disclosing relevant ErbB2 glycan signatures and their functional impact on receptor’s biology in GC cells. The transcriptomic profile of cancer-relevant glycosylation enzymes, and the expression and activation of the ErbB receptors were characterized in four GC cell lines. Cellular- and receptor-specific glycan profiling of ErbB2-overexpressing NCI-N87 cells unveiled a heterogeneous glycosylation pattern harboring the tumor-associated sialyl Lewis a (SLea) antigen. The expression of SLea and key enzymes integrating its biosynthetic pathway were strongly upregulated in this GC cell line. An association between the expression of ERBB2 and FUT3, a central gene in SLea biosynthesis, was disclosed in GC patients, further highlighting the crosstalk between ErbB2 and SLea expression. Moreover, cellular deglycosylation and CA 19.9 antibody-mediated blocking of SLea drastically altered ErbB2 expression and activation in NCI-N87 cells. Altogether, NCI-N87 cell line constitutes an appealing in vitro model to address glycan-mediated regulation of ErbB2 in GC. View Full-Text
Keywords: human epidermal growth factor receptor 2 (ErbB2); gastric cancer (GC); glycosylation; sialyl Lewis a (SLea); CA 19.9 human epidermal growth factor receptor 2 (ErbB2); gastric cancer (GC); glycosylation; sialyl Lewis a (SLea); CA 19.9
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Duarte, H.O.; Balmaña, M.; Mereiter, S.; Osório, H.; Gomes, J.; Reis, C.A. Gastric Cancer Cell Glycosylation as a Modulator of the ErbB2 Oncogenic Receptor. Int. J. Mol. Sci. 2017, 18, 2262.

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