TGF-β1诱导EMT中FOXA2缺失抑制肺腺癌中glcnac n -聚糖合成

IF 3.4 4区 生物学 Q2 BIOCHEMICAL RESEARCH METHODS
Proteomics Pub Date : 2025-03-06 DOI:10.1002/pmic.202400216
Wei Ge, Shengye Wen, Xiaoli Zhou, Yan Chen, Daxiong Zeng, Junhong Jiang, Shuang Yang
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引用次数: 0

摘要

糖基化是一种主要的翻译后修饰(PTM),在癌症中由于糖基转移酶活性的改变而经常失调。研究表明,癌细胞中与上皮-间质转化(EMT)相关的聚糖结构发生了特异性变化。然而,糖基转移酶促进EMT的具体机制尚不清楚。在这项研究中,我们使用肺腺癌(LUAD)患者的支气管肺泡灌洗液(BALF)来比较表征LUAD患者的糖型,并确定LUAD患者糖基转移酶失调。我们发现含有分割GlcNAc结构的n -聚糖显著减少,并通过Western blot证实n -乙酰氨基葡萄糖转移酶- iii (MGAT3)在LUAD中下调。我们观察到,在早期LUAD中,叉头盒蛋白A2 (FOXA2)的信使RNA (mRNA)和蛋白表达均显著下调,FOXA2的缺失作为EMT启动子出现。有趣的是,细胞EMT模型表明,在TGF-β1驱动的EMT过程中,FOXA2缺陷降低了MGAT3的表达,导致LUAD细胞中glcnac n -聚糖水平降低。我们的发现揭示了EMT过程中MGAT3下调和GlcNAc n -聚糖表达的新机制,这一过程对肿瘤转移至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
FOXA2 Loss in TGF-β1-Induced EMT Suppresses Bisecting-GlcNAc N-Glycan Synthesis in Lung Adenocarcinoma

Glycosylation, a major posttranslational modification (PTM), is often dysregulated in cancer due to altered glycosyltransferase activity. Studies have shown specific changes in glycan structures associated with epithelial-mesenchymal transition (EMT) in cancer cells. However, the specific mechanism by which glycosyltransferases contribute to EMT remains unclear. In this study, we used bronchoalveolar lavage fluid (BALF) from lung adenocarcinoma (LUAD) patients to comparatively characterize glycopatterns and identify dysregulated glycosyltransferases in LUAD. We found a significant reduction in N-glycans containing the bisecting GlcNAc structure and confirmed by Western blot that N-acetylglucosaminyltransferase-III (MGAT3) is downregulated in LUAD. We observed a notable downregulation of both messenger RNA (mRNA) and protein expression of Forkhead box protein A2 (FOXA2) in early-stage LUAD, with FOXA2 loss emerging as an EMT promoter. Interestingly, cellular EMT models demonstrated that FOXA2 deficiency decreased MGAT3 expression during TGF-β1-driven EMT, leading to reduced levels of bisecting-GlcNAc N-glycans in LUAD cells. Our findings unveil a novel mechanism underlying the downregulation of MGAT3 and bisecting GlcNAc N-glycan expression during EMT, a process crucial for tumor metastasis.

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来源期刊
Proteomics
Proteomics 生物-生化研究方法
CiteScore
6.30
自引率
5.90%
发文量
193
审稿时长
3 months
期刊介绍: PROTEOMICS is the premier international source for information on all aspects of applications and technologies, including software, in proteomics and other "omics". The journal includes but is not limited to proteomics, genomics, transcriptomics, metabolomics and lipidomics, and systems biology approaches. Papers describing novel applications of proteomics and integration of multi-omics data and approaches are especially welcome.
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