Sialylation of CD55 by ST3GAL1 facilitates immune evasion in cancer

Wen Der Lin, Tan Chi Fan, Jung Tung Hung, Hui Ling Yeo, Sheng Hung Wang, Chu Wei Kuo, Kay Hooi Khoo, Li Mei Pai, John Yu, Alice L. Yu*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

25 引文 斯高帕斯(Scopus)

摘要

Altered glycosylations, which are associated with expression and activities of glycosyltransferases, can dramatically affect the function of glycoproteins and modify the behavior of tumor cells. ST3GAL1 is a sialyltransferase that adds sialic acid to core 1 glycans, thereby terminating glycan chain extension. In breast carcinomas, overexpression of ST3GAL1 promotes tumorigenesis and correlates with increased tumor grade. In pursuing the role of ST3GAL1 in breast cancer using ST3GAL1-siRNA to knockdown ST3GAL1, we identified CD55 to be one of the potential target proteins of ST3GAL1. CD55 is an important complement regulatory protein, preventing cells from complement-mediated cytotoxicity. CD55 had one N-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily O-glycosylated. Detailed analyses of N- and O-linked oligosaccharides of CD55 released from scramble or ST3GAL1 siRNA-treated breast cancer cells by tandem mass spectrometry revealed that the N-glycan profile was not affected by ST3GAL1 silencing. The O-glycan profile of CD55 demonstrated a shift in abundance to nonsialylated core 1 and monosialylated core 2 at the expense of the disialylated core 2 structure after ST3GAL1 silencing. We also demonstrated that O-linked desialylation of CD55 by ST3GAL1 silencing resulted in increased C3 deposition and complement-mediated lysis of breast cancer cells and enhanced sensitivity to antibody-dependent cell-mediated cytotoxicity. These data demonstrated that ST3GAL1-mediated O-linked sialylation of CD55 acts like an immune checkpoint molecule for cancer cells to evade immune attack and that inhibition of ST3GAL1 is a potential strategy to block CD55-mediated immune evasion.

原文英語
頁(從 - 到)113-122
頁數10
期刊Cancer Immunology Research
9
發行號1
DOIs
出版狀態已出版 - 01 01 2021

文獻附註

Publisher Copyright:
© 2020 American Association for Cancer Research.

指紋

深入研究「Sialylation of CD55 by ST3GAL1 facilitates immune evasion in cancer」主題。共同形成了獨特的指紋。

引用此