FUT2 通过增加 LRP1 的岩藻糖基化来抑制结直肠癌的 EMT 和转移。
FUT2 inhibits the EMT and metastasis of colorectal cancer by increasing LRP1 fucosylation.
机构信息
Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Road, Pudong New Area, Shanghai, China.
出版信息
Cell Commun Signal. 2023 Mar 27;21(1):63. doi: 10.1186/s12964-023-01060-0.
BACKGROUND
Fucosyltransferase 2(FUT2) and its induced α-1,2 fucosylation is associated with cancer metastasis. However, the role of FUT2 in colorectal cancer (CRC) metastasis remains unclear.
METHODS
The expression levels and clinical analyses of FUT2 were assessed in CRC samples. Migration and invasion assays, EMT detection, nude mice peritoneal dissemination models and intestinal specific FUT2 knockout mice (FUT2 mice) were used to investigate the effect of FUT2 on metastasis in colorectal cancer. Quantitative proteomics study of glycosylated protein, UEA enrichment, Co-immunoprecipitation identified the mediator of the invasive-inhibiting effects of FUT2.
RESULTS
FUT2 is downregulated in CRC tissues and is positively correlated with the survival of CRC patients. FUT2 is an inhibitor of colorectal cancer metastasis which, when overexpressed, suppresses invasion and tumor dissemination in vitro and in vivo. FUT2 knock-out mice (FUT2 mice) develop AMO and DSS-induced tumors and promote EMT in colorectal cancers. FUT2-induced α-1,2 fucosylation impacts the ability of low-density lipoprotein receptor-related protein 1(LRP1) to suppress colorectal cancer invasion.
CONCLUSIONS
Our study demonstrated that FUT2 induces α-1,2 fucosylation and inhibits EMT and metastasis of colorectal cancer through LRP1 fucosylation, suggesting that FUT2 may serve as a therapeutic target for colorectal cancer. Video Abstract.
背景
岩藻糖基转移酶 2（FUT2）及其诱导的α-1,2 岩藻糖基化与癌症转移有关。然而，FUT2 在结直肠癌（CRC）转移中的作用尚不清楚。
方法
评估 CRC 样本中 FUT2 的表达水平和临床分析。迁移和侵袭实验、上皮间质转化（EMT）检测、裸鼠腹腔扩散模型和肠道特异性 FUT2 敲除小鼠（FUT2 小鼠）用于研究 FUT2 对结直肠癌转移的影响。糖基化蛋白的定量蛋白质组学研究、UEA 富集、免疫共沉淀鉴定了 FUT2 抑制侵袭作用的介体。
结果
FUT2 在 CRC 组织中下调，与 CRC 患者的生存呈正相关。FUT2 是结直肠癌转移的抑制剂，过表达时可抑制体外和体内侵袭和肿瘤扩散。FUT2 敲除小鼠（FUT2 小鼠）可发展 AMO 和 DSS 诱导的肿瘤，并促进结直肠癌的 EMT。FUT2 诱导的α-1,2 岩藻糖基化影响 LDL 受体相关蛋白 1（LRP1）抑制结直肠癌侵袭的能力。
结论
我们的研究表明，FUT2 通过 LRP1 岩藻糖基化诱导α-1,2 岩藻糖基化，抑制 EMT 和结直肠癌转移，提示 FUT2 可能成为结直肠癌的治疗靶点。视频摘要。
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