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

Dall’Olio, Fabio; Malagolini, Nadia; Trinchera, Marco; Chiricolo, Mariella

doi:10.1016/j.bbagen.2014.06.006

Cited by 99 publications

(74 citation statements)

References 236 publications

(232 reference statements)

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“…Moreover, the expression levels of sialyltransferases are known to be much higher in cancer cell lines, to which N2a belongs, than in differentiated cells such as myotubes (reviewed in Refs. 58,59). If the sialylaton status of GPIs within PrP Sc reflects that of PrP C , then the cell-specific differences in sialylation of PrP Sc GPIs might reflect differences in the speed of PrP C trafficking through the Golgi and/or the life time of PrP C in myotubes versus N2a cells.…”

Section: Discussionmentioning

confidence: 99%

Sialylation of Glycosylphosphatidylinositol (GPI) Anchors of Mammalian Prions Is Regulated in a Host-, Tissue-, and Cell-specific Manner

Katorcha

Srivastava

Klimova

et al. 2016

Journal of Biological Chemistry

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Prions or PrPSc are proteinaceous infectious agents that consist of misfolded, self-replicating states of the prion protein or PrP C . PrP C is posttranslationally modified with N-linked glycans and a sialylated glycosylphosphatidylinositol (GPI) anchor. Sc . Remarkably, the proportion of sialo-versus asialo-GPIs was found to be controlled by host, tissue, and cell type but not prion strain. In summary, this study found no strain-specific preferences for selecting PrP C with sialo-versus asialo-GPIs. Instead, this work suggests that the sialylation status of GPIs within PrP Sc is regulated in a cell-, tissue-, or host-specific manner and is likely to be determined by the specifics of GPI biosynthesis.

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Section: Discussionmentioning

confidence: 99%

Sialylation of Glycosylphosphatidylinositol (GPI) Anchors of Mammalian Prions Is Regulated in a Host-, Tissue-, and Cell-specific Manner

Katorcha

Srivastava

Klimova

et al. 2016

Journal of Biological Chemistry

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“…Sialyltransferases constitute an attractive target as they have been shown to underlie aberrant cancer sialylation [113, 114]. For an example, Ferreira et al [114] questioned if the expression of sialyltransferases is different in premalignant and in malignant skin tumors.…”

Section: Aberrant Sialylation In Cancer Progression and Metastasismentioning

confidence: 99%

Neuraminidase-1: A novel therapeutic target in multistage tumorigenesis

2016

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Several of the growth factors and their receptor tyrosine kinases (RTK) such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and insulin are promising candidate targets for cancer therapy. Indeed, tyrosine kinase inhibitors (TKI) have been developed to target these growth factors and their receptors, and have demonstrated dramatic initial responses in cancer therapy. Yet, most patients ultimately develop TKI drug resistance and relapse. It is essential in the clinical setting that the targeted therapies are to circumvent multistage tumorigenesis, including genetic mutations at the different growth factor receptors, tumor neovascularization, chemoresistance of tumors, immune-mediated tumorigenesis and the development of tissue invasion and metastasis. Here, we identify a novel receptor signaling platform linked to EGF, NGF, insulin and TOLL-like receptor (TLR) activations, all of which are known to play major roles in tumorigenesis. The importance of these findings signify an innovative and promising entirely new targeted therapy for cancer. The role of mammalian neuraminidase-1 (Neu1) in complex with matrix metalloproteinase-9 and G protein-coupled receptor tethered to RTKs and TLRs is identified as a major target in multistage tumorigenesis. Evidence exposing the link connecting growth factor-binding and immune-mediated tumorigenesis to this novel receptor-signaling paradigm will be reviewed in its current relationship to cancer.

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“…Either elevated ST6GalNAc1 levels or compromised synthesis of T antigen via mutant Cosmic can raise sTn levels on cancer cells – a direct correlate of progression and poor prognosis (42–44). Malignant activities associated with altered Tn/sTn levels include cell-cell/cell-ECM adhesion, cell migration, cell invasion, and immunoregulation (3, 17, 32, 45). A direct interaction with sTn on cancer cell has recently been established with sialic acid-binding lectin Siglec-15 on macrophages that appears to encourage an immune tolerant cancer microenvironment (46).…”

Section: B α26 Siaylation Of O-glycans and Its Impact On Cancer Promentioning

confidence: 99%

Galectin-Binding O-Glycosylations as Regulators of Malignancy

Dimitroff

2015

Cancer Research

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Cancer cells commonly display aberrant surface glycans and related glycoconjugate scaffolds. Compared with their normal counterparts, cancer cell glycans are variably produced and often structurally distinct, serving as biomarkers of cancer progression or as functional entities to malignancy. The glycan signature of a cancer cell is created by the collaborative activities of glycosyltransferases, glycosidases, nucleotide-sugar transporters, sulfotransferases and glycan-bearing protein/lipid scaffolds. In a coordinated fashion, these factors regulate the synthesis of cancer cell glycans and thus are considered correlates of cancer cell behavior. Functionally, cancer cell glycans can serve as binding targets for endogenous lectin effectors, such as C-type selectins and S-type galectins. There has been a recent surge of important observations on the role of glycosytransferases, specifically α2,6 sialyltransferases, in regulating the length and lectin-binding features of serine/threonine (O)-glycans found on cancer cells. The capping activity of O-glycan-specific α2,6 sialyltransferases, in particular, has been found to regulate cancer growth and metastasis in a galectin-dependent manner. These findings highlight the functional importance of cancer cell O-glycans and related galectin-binding features in the virulent activity of cancer and raise the prospect of targeting cancer cell glycans as effective anti-cancer therapeutics.

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

Abstract: 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.

Cited by 99 publications

References 236 publications

Sialylation of Glycosylphosphatidylinositol (GPI) Anchors of Mammalian Prions Is Regulated in a Host-, Tissue-, and Cell-specific Manner

Sialylation of Glycosylphosphatidylinositol (GPI) Anchors of Mammalian Prions Is Regulated in a Host-, Tissue-, and Cell-specific Manner

Neuraminidase-1: A novel therapeutic target in multistage tumorigenesis

Galectin-Binding O-Glycosylations as Regulators of Malignancy

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