title: Sialosignaling: sialyltransferases as engines of self-fueling loops in cancer progression.
abstract: 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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy. Electronic address: fabio.dallolio@unibo.it.
authors.forename: Fabio
authors.initials: F
authors.lastname: Dall'Olio
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Nadia
authors.initials: N
authors.lastname: Malagolini
authors.affiliation: Department of Medicine Clinical and Experimental (DMCS), University of Insubria Medical School, Varese, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Trinchera
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
authors.forename: Mariella
authors.initials: M
authors.lastname: Chiricolo
mesh_terms: D000818:Animals; D018450:Disease Progression; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009363:Neoplasm Proteins; D012799:Sialyltransferases
keywords: Chemoresistance; Gangliosides; Glycosylation; Integrins; Neural cell adhesion molecule; Sialylation