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Cancer Immunology Research
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Research Articles

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 and Alice L. Yu
Wen-Der Lin
1Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
2Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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Tan-Chi Fan
2Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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Jung‐Tung Hung
2Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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Hui-Ling Yeo
2Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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  • ORCID record for Hui-Ling Yeo
Sheng-Hung Wang
2Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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Chu-Wei Kuo
3Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
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Kay-Hooi Khoo
3Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
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Li-Mei Pai
1Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
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John Yu
2Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
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Alice L. Yu
1Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan.
2Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
4Department of Pediatrics, University of California, San Diego, La Jolla, California.
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  • For correspondence: a1yu@health.ucsd.edu
DOI: 10.1158/2326-6066.CIR-20-0203 Published January 2021
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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 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.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Immunology Research Online (http://cancerimmunolres.aacrjournals.org/).

  • Cancer Immunol Res 2021;9:113–22

  • Received April 2, 2020.
  • Revision received August 13, 2020.
  • Accepted November 3, 2020.
  • Published first November 11, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Immunology Research: 9 (1)
January 2021
Volume 9, Issue 1
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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 and Alice L. Yu
Cancer Immunol Res January 1 2021 (9) (1) 113-122; DOI: 10.1158/2326-6066.CIR-20-0203

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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 and Alice L. Yu
Cancer Immunol Res January 1 2021 (9) (1) 113-122; DOI: 10.1158/2326-6066.CIR-20-0203
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