PT  - JOURNAL ARTICLE
AU  - Lin, Wen-Der
AU  - Fan, Tan-Chi
AU  - Hung, Jung‐Tung
AU  - Yeo, Hui-Ling
AU  - Wang, Sheng-Hung
AU  - Kuo, Chu-Wei
AU  - Khoo, Kay-Hooi
AU  - Pai, Li-Mei
AU  - Yu, John
AU  - Yu, Alice L.
TI  - Sialylation of CD55 by ST3GAL1 Facilitates Immune Evasion in Cancer
AID  - 10.1158/2326-6066.CIR-20-0203
DP  - 2021 Jan 01
TA  - Cancer Immunology Research
PG  - 113--122
VI  - 9
IP  - 1
4099  - http://cancerimmunolres.aacrjournals.org/content/9/1/113.short
4100  - http://cancerimmunolres.aacrjournals.org/content/9/1/113.full
SO  - Cancer Immunol Res2021 Jan 01; 9
AB  - 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.