Sialosignaling: Sialyltransferases as engines of self-fueling loops in cancer progression

被引:100
作者
Dall'Olio, Fabio [1 ]
Malagolini, Nadia [1 ]
Trinchera, Marco [2 ]
Chiricolo, Mariella [1 ]
机构
[1] Univ Bologna, Dept Expt Diagnost & Specialty Med DIMES, I-40126 Bologna, Italy
[2] Univ Insubria, Sch Med, Dept Med Clin & Expt DMCS, Varese, Italy
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2014年 / 1840卷 / 09期
关键词
Glycosylation; Sialylation; Gangliosides; Neural cell adhesion molecule; Integrins; Chemoresistance; HUMAN COLON-CANCER; CELL-ADHESION MOLECULE; GROWTH-FACTOR RECEPTOR; SIALYL-TN ANTIGEN; GALACTOSIDE ALPHA-2,6 SIALYLTRANSFERASE; MESSENGER-RNA EXPRESSION; GD3 SYNTHASE GENE; ALPHA-2,6-SIALYLATED SUGAR CHAINS; EXPERIMENTAL PULMONARY METASTASIS; GANGLIOSIDE-MEDIATED MODULATION;
D O I
10.1016/j.bbagen.2014.06.006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, alpha 2,6-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. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:2752 / 2764
页数:13
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