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深入分析结直肠癌细胞系的 - 聚糖组。

In-Depth Analysis of the -Glycome of Colorectal Cancer Cell Lines.

机构信息

Center for Proteomics and Metabolomics, Leiden University Medical Center, Postbus 9600, 2300 RC Leiden, The Netherlands.

Division of Bioanalytical Chemistry, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.

出版信息

Int J Mol Sci. 2023 Mar 2;24(5):4842. doi: 10.3390/ijms24054842.

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer deaths worldwide. A well-known hallmark of cancer is altered glycosylation. Analyzing the -glycosylation of CRC cell lines may provide potential therapeutic or diagnostic targets. In this study, an in-depth -glycomic analysis of 25 CRC cell lines was conducted using porous graphitized carbon nano-liquid chromatography coupled to electrospray ionization mass spectrometry. This method allows for the separation of isomers and performs structural characterization, revealing profound -glycomic diversity among the studied CRC cell lines with the elucidation of a number of 139 -glycans. A high degree of similarity between the two -glycan datasets measured on the two different platforms (porous graphitized carbon nano-liquid chromatography electrospray ionization tandem mass spectrometry (PGC-nano-LC-ESI-MS) and matrix-assisted laser desorption/ionization time of flight-mass spectrometry (MALDI-TOF-MS)) was discovered. Furthermore, we studied the associations between glycosylation features, glycosyltransferases (GTs), and transcription factors (TFs). While no significant correlations between the glycosylation features and GTs were found, the association between TF CDX1 and (s)Le antigen expression and relevant GTs FUT3/6 suggests that CDX1 contributes to the expression of the (s)Le antigen through the regulation of FUT3/6. Our study provides a comprehensive characterization of the -glycome of CRC cell lines, which may contribute to the future discovery of novel glyco-biomarkers of CRC.

摘要

结直肠癌(CRC)是全球第三大常见癌症,也是癌症死亡的第二大主要原因。癌症的一个众所周知的特征是糖基化改变。分析 CRC 细胞系的-β-糖基化可能提供潜在的治疗或诊断靶点。在这项研究中,使用多孔石墨化碳纳米液相色谱-电喷雾电离质谱联用技术对 25 种 CRC 细胞系进行了深入的-β-糖组学分析。该方法允许异构体分离并进行结构表征,揭示了所研究的 CRC 细胞系中深刻的-β-糖基化多样性,并阐明了 139 种-β-聚糖。在两种不同平台(多孔石墨化碳纳米液相色谱-电喷雾电离串联质谱(PGC-nano-LC-ESI-MS)和基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS))上测量的两种-β-聚糖数据集之间发现了高度相似性。此外,我们研究了糖基化特征、糖基转移酶(GTs)和转录因子(TFs)之间的关联。虽然在糖基化特征和 GTs 之间没有发现显著相关性,但 TF CDX1 与(s)Le 抗原表达和相关 GTs FUT3/6 之间的关联表明,CDX1 通过调节 FUT3/6 促进(s)Le 抗原的表达。我们的研究提供了 CRC 细胞系-β-聚糖组的全面特征,这可能有助于未来发现 CRC 的新型糖生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d358/10003090/8a26169bd148/ijms-24-04842-g001.jpg

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