Overexpression of Cosmc suppresses cell migration and invasion in different subtypes of breast cancer cells via Tn and T glycans
Overexpression of Cosmc suppresses cell migration and invasion in different subtypes of breast cancer cells via Tn and T glycans
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Cosmc 的过表达通过 Tn 和 T 聚糖抑制不同亚型乳腺癌细胞的细胞迁移和侵袭
DOI：
10.1042/bsr20191062
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发表时间：
2020-05
影响因子：
4
通讯作者：
Hongchuan Jiang
中科院分区：
文献类型：
--
作者：
Jun Liu;Feng Xu;Jie Li;Hongchuan Jiang
摘要目的：乳腺癌（BC）的高死亡率与原发性乳腺肿瘤细胞的强转移特性有关。本研究旨在阐明Cosmc对不同分子类型的BC细胞系的生长和转移的影响，这可能与Tn和T聚糖的调节有关。研究方法：利用靶向Cosmc的shRNA或Cosmc过表达质粒转染不同分子类型的BC细胞系，探讨Cosmc在细胞增殖、迁移、侵袭和凋亡中的作用。Western blot检测BC细胞中Tn、T、Cosmc、增殖相关因子（Ki67、PCNA）和凋亡相关因子（Bax、Bad）的蛋白水平。最后，通过体内实验证实了Cosmc的作用。结果：与正常对照组相比，Cosmc在不同亚型的BC细胞系中表达下调。体外实验表明，Cosmc的过表达抑制了BC细胞的增殖、迁移和侵袭，但促进了BC细胞的凋亡。此外，裸鼠体内肿瘤异种移植物显示Cosmc的异位过表达抑制BC细胞的肿瘤生长。因此，BC细胞中增殖相关因子和Tn抗原的水平降低，而增殖相关因子和T抗原的水平升高。该观察结果在异种移植肿瘤中得到体内证实。结论：总体而言，Cosmc的上调可能通过调节Tn和T聚糖之间的平衡来阻碍BC的生长和转移。
Abstract Objectives: The high mortality of breast cancer (BC) is associated with the strong metastatic properties of primary breast tumor cells. The present study was conducted in order to clarify the effect of Cosmc on the growth and metastasis of BC cell lines of different molecular types, which may be implicated in the regulation of Tn and T glycans. Methods: BC cell lines with different molecular types were transduced with shRNA targeting Cosmc or, Cosmc overexpression plasmid in order to explore the role of Cosmc in cell proliferation, migration, invasion, and apoptosis. The protein levels of Tn, T, Cosmc, proliferation-related factors (Ki67 and PCNA) and apoptosis-related factors (Bax and Bad) in BC cell lines were determined by Western blot analyses. Finally, the role of Cosmc was substantiated through in vivo experiments. Results: Cosmc was down-regulated in different subtypes of BC cell lines compared with normal control cells. Overexpression of Cosmc suppressed the proliferation, migration, and invasion, yet promoted the apoptosis of BC cells, as reflected by in vitro experiments. Additionally, in vivo tumor xenografts in nude mice showed that ectopic overexpression of Cosmc inhibited the tumor growth of BC cells. Consequently, the levels of proliferation-related factors and Tn antigen were decreased, while those of apoptosis-related factors and T antigen were increased in BC cells. This observation was confirmed in vivo in xenograft tumors. Conclusion: Collectively, up-regulation of Cosmc potentially impedes BC growth and metastasis by modulating the balance between Tn and T glycans.
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