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52. Li Jia, Jun Li, Pengfei Li, Didi Liu, Jing Li, Jiechen Shen, Bojing Zhu, Chen Ma, Ting Zhao, Rongxia Lan, Liuyi Dang, Wang Li, Shisheng Sun*. Site-specific glycoproteomic analysis revealing increased core-fucosylation on FOLR1 enhances folate uptake capacity of HCC cells to promote EMT. Theranostics. 2021, 11 (14): 6905-6921.
点击次数：
影响因子：11.556
DOI码：10.7150/thno.56882
关键字：FOLR1; core-fucosylation; epithelial-mesenchymal transition; glycoproteome; hepatocellular carcinoma.
摘要：Rationale: Epithelial-mesenchymal transition (EMT) has been recognized as an important step toward high invasion and metastasis of many cancers including hepatocellular carcinoma (HCC), while the mechanism for EMT promotion is still ambiguous. Methods: The dynamic alterations of site-specific glycosylation during HGF/TGF-β1-induced EMT process of three HCC cell lines were systematically investigated using precision glycoproteomic methods. The possible roles of EMT-related glycoproteins and site-specific glycans were further confirmed by various molecular biological approaches. Results: Using mass spectrometry-based glycoproteomic methods, we totally identified 2306 unique intact glycopeptides from SMMC-7721 and HepG2 cell lines, and found that core-fucosylated glycans were accounted for the largest proportion of complex N-glycans. Through quantification analysis of intact glycopeptides, we found that the majority of core-fucosylated intact glycopeptides from folate receptor α (FOLR1) were up-regulated in the three HGF-treated cell lines. Similarly, core-fucosylation of FOLR1 were up-regulated in SMMC-7721 and Hep3B cells with TGF-β1 treatment. Using molecular approaches, we further demonstrated that FUT8 was a driver for HGF/TGF-β1-induced EMT. The silencing of FUT8 reduced core-fucosylation and partially blocked the progress of HGF-induced EMT. Finally, we confirmed that the level of core-fucosylation on FOLR1 especially at the glycosite Asn-201 positively regulated the cellular uptake capacity of folates, and enhanced uptake of folates could promote the EMT of HCC cells. Conclusions: Based on the results, we proposed a potential pathway for HGF or TGF-β1-induced EMT of HCC cells: HGF or TGF-β1 treatment of HCC cells can increase the expression of glycosyltransferase FUT8 to up-regulate the core-fucosylation of N-glycans on glycoproteins including the FOLR1; core-fucosylation on FOLR1 can then enhance the folate uptake capacity to finally promote the EMT progress of HCC cells.
论文类型：期刊论文
学科门类：理学
一级学科：生物学
是否译文：否
收录刊物：SCI
上一条：53. Jiechen Shen#, Li Jia#, Liuyi Dang#, Yuanjie Su#, Jie Zhang, Yintai Xu, Bojing Zhu, Zexuan Chen, Jingyu Wu, Rongxia Lan, Zhifang Hao, Chen Ma, Ting Zhao, Ni Gao, Jieyun Bai, Yuan Zhi, Jun Li, Junying Zhang, Shisheng Sun*. StrucGP: de novo structural sequencing of site-specific N-glycan on glycoproteins using a modularization strategy. Nature Methods. 2021, 18: 921-929.
下一条：51. Pengfei Li#, Zhifang Hao#, Jingyu Wu, Chen Ma, Yintai Xu, Jun Li, Rongxia Lan, Bojing Zhu, Pengyu Ren, Daidi Fan, Shisheng Sun*. Comparative Proteomic Analysis of Polarized Human THP-1 and Mouse RAW264. 7 Macrophages. Frontiers in immunology. 2021, 12: 700009.