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核心 1 半乳糖转移酶的抑制与人类结肠癌细胞中 TF 的减少和 Tn、唾液酸化-Tn 和核心 3 聚糖的反式增加有关。

Suppression of core 1 Gal-transferase is associated with reduction of TF and reciprocal increase of Tn, sialyl-Tn and Core 3 glycans in human colon cancer cells.

机构信息

Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.

出版信息

PLoS One. 2013;8(3):e59792. doi: 10.1371/journal.pone.0059792. Epub 2013 Mar 25.

DOI:10.1371/journal.pone.0059792
PMID:23536887
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3607565/
Abstract

It has long been presumed, though with surprisingly little evidence, a competition between Core 1 Gal-transferase (C1GalT), Core 3 GlcNAc-transferase (C3GnT) and sialyl-transferase (ST6GalNAc-T) for elongation of O-linked mucin-type glycans initiated with GalNAcα-Ser/Thr. This study tested this presumption by selective suppression of one of these glycosyltransferases and then analysed the expressions of the enzymatic products of the other three glycosyltransferases. It was found that siRNA suppression of C1GalT markedly reduced the expression of Galβ1,3GalNAcα- (Core 1) and in the meantime increased the expressions of sialyl-GalNAcα- (sialyl-Tn), GalNAcα- (Tn) and GlcNAcβ1,3GalNAcα- (Core 3)-associated glycans in human colon cancer HT29 and SW620 cells. This supports a competitive modification of the GalNAcα-Ser/Thr between C1GalT, C3GnT and ST6GalNAc-T in O-glycan biosynthesis. As Tn, TF and sialyl-Tn are oncofetal antigens and are over-expressed in most human cancers, this information is useful for the development of glycosyltransferase-targeted therapeutic strategies for cancer treatment.

摘要

长期以来，人们一直假设，尽管证据惊人地缺乏，Core 1 Gal-transferase（C1GalT）、Core 3 GlcNAc-transferase（C3GnT）和唾液酸转移酶（ST6GalNAc-T）之间存在竞争，以延长以 GalNAcα-Ser/Thr 起始的 O-连接粘蛋白型聚糖的延伸。本研究通过选择性抑制其中一种糖基转移酶来检验这一假设，然后分析其他三种糖基转移酶的酶产物的表达。结果发现，C1GalT 的 siRNA 抑制显著降低了 Galβ1,3GalNAcα-（Core 1）的表达，同时增加了人结肠癌细胞 HT29 和 SW620 中唾液酰-GalNAcα-（sialyl-Tn）、GalNAcα-（Tn）和 GlcNAcβ1,3GalNAcα-（Core 3）相关聚糖的表达。这支持了 C1GalT、C3GnT 和 ST6GalNAc-T 在 O-聚糖生物合成中对 GalNAcα-Ser/Thr 的竞争性修饰。由于 Tn、TF 和 sialyl-Tn 是癌胚抗原，在大多数人类癌症中过度表达，因此这些信息对于开发针对糖基转移酶的治疗策略治疗癌症是有用的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccc/3607565/265f4745fdc8/pone.0059792.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccc/3607565/5b23c67d0d5b/pone.0059792.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccc/3607565/b8236f1dc164/pone.0059792.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccc/3607565/440a2a8abd2f/pone.0059792.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccc/3607565/265f4745fdc8/pone.0059792.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccc/3607565/5b23c67d0d5b/pone.0059792.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccc/3607565/b8236f1dc164/pone.0059792.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccc/3607565/440a2a8abd2f/pone.0059792.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ccc/3607565/265f4745fdc8/pone.0059792.g004.jpg

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