Sialosignaling: sialyltransferases as engines of self-fueling loops in cancer progression.
BACKGROUND
Glycosylation 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 REVIEW
To 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 CONCLUSIONS
We 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 SIGNIFICANCE
Sialyltransferases 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.
["Dall'Olio|Fabio|F|", 'Malagolini|Nadia|N|', 'Trinchera|Marco|M|', 'Chiricolo|Mariella|M|']
D000818:Animals D018450:Disease Progression D006801:Humans D009363:Neoplasm Proteins D009369:Neoplasms D012799:Sialyltransferases D015398:Signal Transduction
Glycosylation Sialylation Gangliosides Chemoresistance Integrins Neural cell adhesion molecule