Glicosilação de células de cancro gástrico como modulador do receptor oncogénico ErbB2

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Glicosilação de células de cancro gástrico como modulador do receptor oncogénico ErbB2

Quinta, 22.02.2018

Autores e Afiliações:

Henrique O. Duarte1,2,3, Meritxell Balmaña1,2, Stefan Mereiter1,2, Hugo Osório1,2,4, Joana Gomes1,2 and Celso A. Reis1,2,3,4

1Institute for Research and Innovation in Health (i3S), University of Porto, 4200-135 Porto, Portugal

2Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal

3Instituto de Ciências Biomédicas Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal

4Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal



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.



Revista: International Journal of Molecular Sciences, Volume 18, Issue 11