Data from Sialylation of CD55 by ST3GAL1 Facilitates Immune Evasion in Cancer

Abstract

<div>Abstract<p>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 <i>ST3GAL1</i>-siRNA to knockdown <i>ST3GAL1</i>, 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 <i>N</i>-linked glycosylation site in addition to a Ser/Thr-rich domain, which was expected to be heavily <i>O</i>-glycosylated. Detailed analyses of <i>N</i>- and <i>O</i>-linked oligosaccharides of CD55 released from scramble or <i>ST3GAL1</i> siRNA–treated breast cancer cells by tandem mass spectrometry revealed that the <i>N</i>-glycan profile was not affected by <i>ST3GAL1</i> silencing. The <i>O</i>-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 <i>ST3GAL1</i> silencing. We also demonstrated that <i>O</i>-linked desialylation of CD55 by <i>ST3GAL1</i> 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 <i>O</i>-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.</p></div>