FUT2介导岩藻糖基化修饰调控Wnt/β-catenin信号促进肺腺癌发生发展的作用机制及诊断价值研究
批准号:
82002234
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
范赛荣
依托单位:
学科分类:
分子生物学检验
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
范赛荣
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中文摘要
岩藻糖基化是最常见的糖基化修饰之一,与肿瘤的发生发展密切相关,在肿瘤早期筛查及治疗方面具有重要的作用及广泛的应用前景。课题组前期研究发现岩藻糖基转移酶2(FUT2)在肺腺癌中特异性表达,能促进肺腺癌细胞的增殖、迁移侵袭能力,且能影响β-catenin信号传导及其下游靶基因的表达,提示FUT2可能通过调控Wnt/β-catenin信号通路,进而促进肺腺癌的形成与转移。本课题拟在前期工作基础上,从FUT2与Wnt/β-catenin信号通路的相互调控作用出发,明确FUT2及其介导的糖基化修饰与β-catenin信号异常传导的双向调控作用,阐明FUT2促进肺腺癌进展的分子机制。同时从血清学、细胞学等多层次入手,利用Co-IP联合凝集素结合生物信息学分析明确FUT2及其靶蛋白在肺腺癌诊疗中的应用价值。实现从基础到临床,系统阐述FUT2及其介导糖基化修饰在肺腺癌进展中的意义和诊疗价值。
英文摘要
Fucosylation, one of the most common glycosylation, plays an important role in tumor’s development and progression, and has extensive application in early diagnosis and treatment of tumors. Our previous studies showed that fucosyltransferase 2 (FUT2) was abnormally expressed in lung adenocarcinoma (LUAD), and promoted the proliferation, migration and invasion of lung adenocarcinoma cells, which was associated with the altered β-catenin signal transduction and the expression of downstream target genes, indicating that FUT2 can regulate the Wnt/β-catenin signal pathway, and promote LUAD formation and metastasis. In this project, based on our previous study, we will explore the bidirectional relationship between the expression of FUT2 (or fucosylation induced by FUT2) and Wnt/β-catenin signal transduction, and clarify the role of FUT2 in the development of LUAD. Meanwhile, the experiments will be performed in multiple levels, including serology and cytology, and the methods, such as Co-IP/Lectin and bioinformatics, will be used to investigate the target protein of FUT2, and examine the ability of the identified biomarkers to diagnose the patients with LUAD. Taken together, this study will elucidate the mechanism at the base of FUT2 capability to promote the progression of LUAD, and may provide potential biomarkers and therapeutic targets for lung adenocarcinoma.
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DOI:10.3390/cells11244031
发表时间:2022-12-13
期刊:Cells
影响因子:6
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