The Distinct Roles of Sialyltransferases in Cancer Biology and Onco-Immunology

Abstract

Aberrant glycosylation is a key feature of malignant transformation. Hypersialylation, the enhanced expression of sialic acid-terminated glycoconjugates on the cell surface, has been linked to immune evasion and metastatic spread, eventually by interaction with sialoglycan-binding lectins, including Siglecs and selectins. The biosynthesis of tumor-associated sialoglycans involves sialyltransferases, which are differentially expressed in cancer cells. In this review article, we provide an overview of the twenty human sialyltransferases and their roles in cancer biology and immunity. A better understanding of the individual contribution of select sialyltransferases to the tumor sialome may lead to more personalized strategies for the treatment of cancer.

A novel ganglioside-related risk signature can reveal the distinct immune landscape of neuroblastoma and predict the immunotherapeutic response

“…Notably, NEU4 has been identified as a potential regulator of neuronal development, with overexpression promoting the acquisition of a stem cell-like phenotype in neuroblastoma cells ( 53 ). The sialyltransferases are required to synthesize gangliosides, and their aberrant expression is closely related to a poor prognosis in tumors ( 54 , 55 ). Among them, ST3GAL1 overexpression promotes epithelial-mesenchymal transition, migration, and invasion in ovarian cancer ( 56 ), and ST3GAL3 downregulation inhibits pancreatic cancer cell migration and invasion ( 57 ).…”

Renovation as innovation: Repurposing human antibacterial peptide LL-37 for cancer therapy

“…Moreover, as AMPs bind with bacterial membranes, ACPs can bind directly with the cancer cell walls due to their cationic and amphipathic nature ( Ma et al, 2019 ). It has been established that different from normal eukaryotic cell membranes which are made of uncharged neutral phospholipids, sphingomyelins, and cholesterol and are neutral in charge ( Zachowski, 1993 ; Doktorova et al, 2020 ), the surface of the cancer cells is net negatively charged because of increased proportions of anionic phosphatidylserine, heparan, and chondroitin sulfate proteoglycans, O-glycosylated mucins, and sialylated glycoproteins ( Warren, 1974 ; Warren et al, 1979 ; Utsugi et al, 1991 ; Zwaal et al, 2005 ; Calianese and Birge, 2020 ; Brockhausen and Melamed, 2021 ; Hassan et al, 2021 ; Hugonnet et al, 2021 ). ACPs can selectively recognize cancer cells by electrostatic interactions with the negatively charged phospholipids on the surface.…”

Lipoprotein sialylation in atherosclerosis: Lessons from mice

“…Glycosyltransferases are also closely involved in the key events in the early stage of atherosclerosis, including generation of functional selectin ligands and regulation of leukocyte adhesion to the endothelium and subsequent extravasation ( 100 – 102 ). Mammalian sialyltransferases comprise 20 glycosyltransferases that facilitate the transfer of sialic acids to the terminal glycosyl group of glycoproteins and glycolipids ( 69 , 103 ). Sialic acid is attached to the glycan terminus through three different linkages, namely, α2,3, α2,6, or α2,8, which are formed by the distinct sets of sialyltransferases.…”