Sialylation of CD55 by ST3GAL1 Facilitates Immune Evasion in Cancer
- 1 January 2021
- journal article
- research article
- Published by American Association for Cancer Research (AACR) in Cancer Immunology Research
- Vol. 9 (1), 113-122
- https://doi.org/10.1158/2326-6066.cir-20-0203
Abstract
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 non-sialylated core 1 and monosialylated core 2, at the expenses of 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.Other Versions
Funding Information
- Ministry of Science and Technology (MOST 103-2321-B-182A-005, MOST 104-2321-B-182A-003, MOST 105-2321-B-182A-001, OMRPG3C0014)
- Ministry of Science and Technology (MOST 106-3114-B-182A-001, MOST 107-2321-B-182A-005, MOST 108-2321-B-182A-004, MOST 109-2321-B-182A-005)
- Ministry of Science and Technology (CMRPG3G1531-CMRPG3G1533)
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