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Differential expression of alpha-2,3-sialyltransferases and alpha-1,3/4-fucosyltransferases regulates the levels of sialyl Lewis a and sialyl Lewis x in gastrointestinal carcinoma cells

Title
Differential expression of alpha-2,3-sialyltransferases and alpha-1,3/4-fucosyltransferases regulates the levels of sialyl Lewis a and sialyl Lewis x in gastrointestinal carcinoma cells
Type
Article in International Scientific Journal
Year
2010
Authors
Carvalho AS
(Author)
FMUP
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Harduin-Lepers A
(Author)
Other
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Magalhães AM
(Author)
Other
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Machado E
(Author)
Other
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Mendes N
(Author)
FMUP
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Costa LT
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Matthiesen R
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Almeida R
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FMUP
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Costa J
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Celso Reis
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FMUP
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Journal
Vol. 42 No. 11
Pages: 80-89
ISSN: 1357-2725
Publisher: Elsevier
Scientific classification
FOS: Medical and Health sciences > Other medical sciences
CORDIS: Health sciences
Other information
Authenticus ID: P-003-BBE
Abstract (EN): Sialyl Lewis x and sialyl Lewis a expression depends on sialyltransferases and fucosyltransferases. In this study, we screened for major variations of sialyltransferases and fucosyltransferases involved in the synthesis and regulation of sialyl Lewis x and sialyl Lewis a epitopes in gastrointestinal carcinoma cells. Our results show that expression of ST3Gal IV in several gastrointestinal cell lines is correlated with the expression of sialyl Lewis x at the cell surface. ST3Gal IV overexpressed in the gastric MKN45 cell line, showed exclusive enzymatic activity towards glycoproteins containing terminal Gal beta 1-4GlcNAc structure. On the other hand, when ST3Gal III was overexpressed in MKN45, an increase in the expression levels of both sialyl Lewis epitopes was observed. ST3Gal III and ST3Gal IV lead to de novo synthesis of sialyl Lewis x determinant on different molecular weight glycoproteins of MKN45 cells suggesting that each enzyme used different substrates within the available glycoproteome. The final glycosylation step in sialyl Lewis x and sialyl Lewis a biosynthesis in MKN45 cell line was shown to be associated to FUT5, which efficiently fucosylated sialyl Lewis precursors on glycoproteins. Moreover we demonstrate that the expression of sialyl Lewis epitopes in the MKN45 was induced by cell confluence, which can be regarded as a model to study altered glycosylation during turnout progression. This increase was observed together with an increase in mRNA levels of ST-3GAL3, FUT5 and FUT6, and a decrease in FUT transcript levels in MKN45 confluent cells, suggesting a possible control at the transcriptional level.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 10
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