Loss and recovery of Mgat3 and GnT-III Mediated E-cadherin N-glycosylation is a mechanism involved in epithelial-mesenchymal-epithelial transitions.
Loss and recovery of Mgat3 and GnT-III Mediated E-cadherin N-glycosylation is a mechanism involved in epithelial-mesenchymal-epithelial transitions.
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DOI：
10.1371/journal.pone.0033191
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Oliveira C
中科院分区：
文献类型：
--
作者：
Pinho SS;Oliveira P;Cabral J;Carvalho S;Huntsman D;Gärtner F;Seruca R;Reis CA;Oliveira C
N-乙酰葡糖胺转移酶-III（GnT-III）是一种由Mgat 3编码的糖基转移酶，可催化β 1，4-二等分-N-乙酰葡糖胺在N-聚糖上的加成。GnT-III被认为是一种转移抑制剂，对细胞粘附和迁移具有不同的影响。我们先前已经描述了存在一个功能性的反馈环之间的E-钙粘蛋白的表达和GnT-III介导的糖基化。GnT-III介导的糖基化对E-钙粘蛋白表达和细胞表型的影响使我们评估Mgat 3和GnT-III糖基化在上皮-间充质转化（EMT）和逆转过程间充质-上皮转化（MET）中的作用。我们分析了在EMT/MET过程中控制Mgat 3表达以及GnT-III介导的糖基化的表达谱和遗传机制，一般情况下，特别是E-钙粘蛋白。我们发现，在EMT过程中，Mgat 3的表达显着下降，后来恢复时，细胞恢复到上皮样表型。我们进一步确定了Mgat 3启动子甲基化/去甲基化参与了这种表达调控。Mgat 3表达变化的影响，沿着EMT/MET，导致GnT-III的酶促产物（二等分GlcNAc结构）的表达水平的变化，更重要的是，导致E-钙粘蛋白糖基化与二等分GlcNAc结构的特异性修饰。总之，这项工作首次鉴定了Mgat 3糖基因表达和GnT-III介导的糖基化，特别是在E-钙粘蛋白上，作为EMT/MET机制签名的一种新的主要成分，支持其在EMT/MET期间的作用。
N-acetylglucosaminyltransferase-III (GnT-III) is a glycosyltransferase encoded by Mgat3 that catalyzes the addition of β1,4-bisecting-N-acetylglucosamine on N-glycans. GnT-III has been pointed as a metastases suppressor having varying effects on cell adhesion and migration. We have previously described the existence of a functional feedback loop between E-cadherin expression and GnT-III-mediated glycosylation. The effects of GnT-III-mediated glycosylation on E-cadherin expression and cellular phenotype lead us to evaluate Mgat3 and GnT-III-glycosylation role during Epithelial-Mesenchymal-Transition (EMT) and the reverted process, Mesenchymal-Epithelial-Transition (MET). We analyzed the expression profile and genetic mechanism controlling Mgat3 expression as well as GnT-III-mediated glycosylation, in general and specifically on E-cadherin, during EMT/MET. We found that during EMT, Mgat3 expression was dramatically decreased and later recovered when cells returned to an epithelial-like phenotype. We further identified that Mgat3 promoter methylation/demethylation is involved in this expression regulation. The impact of Mgat3 expression variation, along EMT/MET, leads to a variation in the expression levels of the enzymatic product of GnT-III (bisecting GlcNAc structures), and more importantly, to the specific modification of E-cadherin glycosylation with bisecting GlcNAc structures. Altogether, this work identifies for the first time Mgat3 glycogene expression and GnT-III-mediated glycosylation, specifically on E-cadherin, as a novel and major component of the EMT/MET mechanism signature, supporting its role during EMT/MET.
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影响因子：
11.2
作者：
Song, Yinghui;Aglipay, Jason A.;Stanley, Pamela
通讯作者：
Stanley, Pamela
影响因子：
2.9
作者：
Robson, Ewan J. D.;Khaled, Walid T.;Watson, Christine J.
通讯作者：
Watson, Christine J.
影响因子：
4.8
作者：
Yoshimura, M;Ihara, Y;Taniguchi, N
通讯作者：
Taniguchi, N
影响因子：
3
作者：
Gu, JG;Taniguchi, N
通讯作者：
Taniguchi, N
DOI：
10.1073/pnas.92.19.8754
发表时间：
1995-09-12
影响因子：
11.1
作者：
YOSHIMURA, M;NISHIKAWA, A;TANIGUCHI, N
通讯作者：
TANIGUCHI, N