N-acetylglucosaminyltransferase V drives colorectal cancer metastasis by facilitating ZO-1 ubiquitination and degradation.

IF 5.3 2区医学 Q1 ONCOLOGY Cancer Cell International Pub Date : 2024-11-07 DOI:10.1186/s12935-024-03551-7

Yueping Zhan, Chenjun Huang, Rong Wang, Xiao Xiao, Xuewen Xu, Chunfang Gao

{"title":"N-acetylglucosaminyltransferase V drives colorectal cancer metastasis by facilitating ZO-1 ubiquitination and degradation.","authors":"Yueping Zhan, Chenjun Huang, Rong Wang, Xiao Xiao, Xuewen Xu, Chunfang Gao","doi":"10.1186/s12935-024-03551-7","DOIUrl":null,"url":null,"abstract":"<p><p>Increasing evidence supports the crucial role of Epithelial-Mesenchymal Transition (EMT) in cancer invasion and metastasis. N-acetylglucosaminyltransferase V (MGAT5), which is associated with multiantenna glycosylation, can contribute to tumorigenesis, yet its specific role in promoting colorectal cancer (CRC) metastasis remains unclear. Bioinformatics analysis of CRC datasets revealed that elevated MGAT5 expression was associated with EMT and a poor prognosis. In vitro experiments confirmed the pivotal role of MGAT5 as an EMT regulator in CRC cells. MGAT5 overexpression stimulated cell proliferation and migration, while MGAT5 knockdown had the opposite effect. Mechanistically, MGAT5 promoted EMT through multiantenna glycosylation of ZO-1, promoting its ubiquitination and reducing its expression. Clinically, MGAT5 upregulation in the CRC TMA correlated negatively with ZO-1 expression, which is indicative of malignancy and a poor prognosis. This study revealed that MGAT5 promotes EMT in CRC via interactions between multiple antenna glycosylation products and ZO-1 ubiquitination/degradation, indicating that MGAT5 could serve as a promising therapeutic target for CRC.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"24 1","pages":"366"},"PeriodicalIF":5.3000,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545198/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-024-03551-7","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Increasing evidence supports the crucial role of Epithelial-Mesenchymal Transition (EMT) in cancer invasion and metastasis. N-acetylglucosaminyltransferase V (MGAT5), which is associated with multiantenna glycosylation, can contribute to tumorigenesis, yet its specific role in promoting colorectal cancer (CRC) metastasis remains unclear. Bioinformatics analysis of CRC datasets revealed that elevated MGAT5 expression was associated with EMT and a poor prognosis. In vitro experiments confirmed the pivotal role of MGAT5 as an EMT regulator in CRC cells. MGAT5 overexpression stimulated cell proliferation and migration, while MGAT5 knockdown had the opposite effect. Mechanistically, MGAT5 promoted EMT through multiantenna glycosylation of ZO-1, promoting its ubiquitination and reducing its expression. Clinically, MGAT5 upregulation in the CRC TMA correlated negatively with ZO-1 expression, which is indicative of malignancy and a poor prognosis. This study revealed that MGAT5 promotes EMT in CRC via interactions between multiple antenna glycosylation products and ZO-1 ubiquitination/degradation, indicating that MGAT5 could serve as a promising therapeutic target for CRC.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

N-乙酰葡糖胺基转移酶V通过促进ZO-1的泛素化和降解来推动结直肠癌转移。

越来越多的证据支持上皮-间质转化（EMT）在癌症侵袭和转移中的关键作用。与多天线糖基化相关的N-乙酰葡糖胺基转移酶V（MGAT5）可促进肿瘤发生，但它在促进结直肠癌（CRC）转移中的具体作用仍不清楚。对 CRC 数据集进行的生物信息学分析表明，MGAT5 表达的升高与 EMT 和不良预后有关。体外实验证实了 MGAT5 在 CRC 细胞中作为 EMT 调节因子的关键作用。MGAT5过表达刺激细胞增殖和迁移，而MGAT5敲除则产生相反的效果。从机制上讲，MGAT5 通过对 ZO-1 进行多天线糖基化，促进其泛素化并降低其表达，从而促进 EMT。临床上，MGAT5在CRC TMA中的上调与ZO-1的表达呈负相关，而ZO-1的表达预示着恶性程度和不良预后。这项研究揭示了MGAT5通过多种天线糖基化产物与ZO-1泛素化/降解之间的相互作用促进了CRC的EMT，表明MGAT5可作为CRC的一个有前景的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Cancer Cell International ONCOLOGY-

CiteScore

10.90

自引率

1.70%

发文量

360

审稿时长

1 months

期刊介绍： Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques. The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors. Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.