Differential expression of α-2,3-sialyltransferases and α-1,3/4-fucosyltransferases regulates the levels of sialyl Lewis a and sialyl Lewis x in gastrointestinal carcinoma cells
Differential expression of α-2,3-sialyltransferases and α-1,3/4-fucosyltransferases regulates the levels of sialyl Lewis a and sialyl Lewis x in gastrointestinal carcinoma cells
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DOI：
10.1016/j.biocel.2009.09.010
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发表时间：
2010-01-01
影响因子：
4
通讯作者：
Reis, C. A.
中科院分区：
文献类型：
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作者：
Carvalho, A. S.;Harduin-Lepers, A.;Reis, C. A.
唾液酸刘易斯x和唾液酸刘易斯a的表达依赖于唾液酸转移酶和岩藻糖基转移酶。在这项研究中，我们筛选了唾液酸转移酶和岩藻糖基转移酶的主要变化，参与合成和调节唾液酸刘易斯x和唾液酸刘易斯a表位在胃肠道癌细胞。我们的研究结果表明，ST 3 Gal IV在几种胃肠道细胞系中的表达与细胞表面的sialyl刘易斯x的表达相关。在胃MKN 45细胞系中过表达的ST 3Gal IV对含有末端Gal β 1-4GlcNAc结构的糖蛋白显示出排他性的酶活性。另一方面，当ST 3Gal III在MKN 45中过表达时，观察到两种唾液酸刘易斯表位的表达水平增加。ST 3Gal III和ST 3Gal IV导致MKN 45细胞的不同分子量糖蛋白上的唾液酸刘易斯x决定簇的从头合成，这表明每种酶在可用的糖蛋白组内使用不同的底物。MKN 45细胞系中sialyl刘易斯x和sialyl刘易斯a生物合成中的最终糖基化步骤显示与FUT 5相关，FUT 5有效地岩藻糖基化糖蛋白上的sialyl刘易斯前体。此外，我们证明了唾液酸刘易斯表位在MKN 45中的表达是由细胞融合诱导的，这可以被视为研究在turnout进展过程中改变的糖基化的模型。在MKN 45融合细胞中观察到这种增加以及ST-3GAL 3、FUT 5和FUT 6的mRNA水平增加和FUT转录物水平降低，表明可能在转录水平上进行控制。(C)2009爱思唯尔有限公司保留所有权利。
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. (C) 2009 Elsevier Ltd. All rights reserved.