Sialosignaling: Sialyltransferases as engines of self-fueling loops in cancer progression |
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Authors: | Fabio Dall'Olio Nadia Malagolini Marco Trinchera Mariella Chiricolo |
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Affiliation: | 1. Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;2. Department of Medicine Clinical and Experimental (DMCS), University of Insubria Medical School, Varese, Italy |
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Abstract: | BackgroundGlycosylation is increasingly recognized as one of the most relevant postranslational modifications. Sialic acids are negatively charged sugars which frequently terminate the carbohydrate chains of glycoproteins and glycolipids. The addition of sialic acids is mediated by sialyltransferases, a family of glycosyltransferases with a crucial role in cancer progression.Scope of the reviewTo describe the phenotypic and clinical implications of altered expression of sialyltransferases and of their cognate sialylated structures in cancer. To propose a unifying model of the role of sialyltransferases and sialylated structures on cancer progression.Major conclusionsWe first discuss the biosynthesis and the role played by the major cancer-associated sialylated structures, including Thomsen–Friedenreich-associated antigens, sialyl Lewis antigens, α2,6-sialylated lactosamine, polysialic acid and gangliosides. Then, we show that altered sialyltransferase expression in cancer, consequence of genetic and epigenetic alterations, generates a flow of information toward the membrane through the biosynthesis of aberrantly sialylated molecules (inside-out signaling). In turn, the presence of aberrantly sialylated structures on cell membrane receptors generates a flow of information toward the nucleus, which can exacerbate the neoplastic phenotype (outside-in signaling). We provide examples of self-fueling loops generated by these flows of information.General significanceSialyltransferases have a wide impact on the biology of cancer and can be the target of innovative therapies. Our unified view provides a conceptual framework to understand the impact of altered glycosylation in cancer. |
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Keywords: | ALL, acute lymphocytic leukemia AML, acute myeloblastic leukemia 5-AZA, 5&prime -azacytidine BCG, Bacillus Calmette&ndash Guerin CIN, chromosome instability DP, degree of polymerization ECM, extracellular matrix EGF, epidermal growth factor EGFR, epidermal growth factor receptor EMT, epithelial to mesenchymal transition ER, estrogen receptors ERE, estrogen responsive element ERK, extracellular signal-regulated kinase FAK, focal adhesion kinase Gal, Galactose GalNAc, N-acetylgalactosamine GlcNAc, N-acetylglucosamine MAPK, mitogen-activated protein kinase MSI, microsatellite instability MSS, microsatellite stability MUC1, mucin-1 N-CAM, neural cell adhesion molecule PCR, polymerase chain reaction PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase PIP3, phosphatidylinositol (3,4,5)-triphosphate PSA, polysialic acid PST, polysialyltransferase ST8SIA4 Sia, sialic acid sT, sialyl-T sTn, sialyl-Tn Sia6LacNAc, α2,6-sialylated lactosamine SNA, Sambucus nigra agglutinin STX, polysialyltransferase ST8SIA2 TF, Thomsen&ndash Friedenreich sLea, sialyl-Lewisa sLex, sialyl-Lewisx TGF-β, transforming growth factor-β TNF-α, tumor necrosis factor-α VEGF, vascular endothelial growth factor VEGFR, vascular endothelial growth factor receptor |
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