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

Duarte, Henrique O ; Balmaña, Meritxell ; Mereiter, Stefan ; Osório, Hugo ; Gomes, Joana ; Reis, Celso A

International journal of molecular sciences, 2017-10, Vol.18 (11), p.2262 [Periódico revisado por pares]

Switzerland: MDPI AG

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Título:
Gastric Cancer Cell Glycosylation as a Modulator of the ErbB2 Oncogenic Receptor
Autor: Duarte, Henrique O ; Balmaña, Meritxell ; Mereiter, Stefan ; Osório, Hugo ; Gomes, Joana ; Reis, Celso A
Assuntos: Aberration ; Activation ; Biosynthesis ; CA 19.9 ; Crosstalk ; Deglycosylation ; Enzymes ; Epidermal growth factor ; ErbB protein ; ErbB-2 protein ; Gastric cancer ; gastric cancer (GC) ; Gene expression ; Glycan ; Glycosylation ; Growth factors ; Guanylate cyclase ; human epidermal growth factor receptor 2 (ErbB2) ; Molecular biology ; Molecular modelling ; sialyl Lewis a (SLea) ; Sialyl Lewis a antigen ; Tumorigenesis
É parte de: International journal of molecular sciences, 2017-10, Vol.18 (11), p.2262
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SourceType-Scholarly Journals-1
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Descrição: 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 (SLe ) antigen. The expression of SLe and key enzymes integrating its biosynthetic pathway were strongly upregulated in this GC cell line. An association between the expression of and , a central gene in SLe biosynthesis, was disclosed in GC patients, further highlighting the crosstalk between ErbB2 and SLe expression. Moreover, cellular deglycosylation and CA 19.9 antibody-mediated blocking of SLe 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.
Editor: Switzerland: MDPI AG
Idioma: Inglês

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

Duarte, Henrique O ; Balmaña, Meritxell ; Mereiter, Stefan ; Osório, Hugo ; Gomes, Joana ; Reis, Celso A

Switzerland: MDPI AG

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