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Dall’Olio, Fabio; Chiricolo, Mariella

doi:10.1023/a:1022288022969

Cited by 247 publications

(108 citation statements)

References 140 publications

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“…Proteolytically untethered ST6Gal-1 is subsequently released into systemic circulation, where it has been generally regarded as a by-product of metabolic inefficiency without significant physiologic function, although circulatory ST6Gal-1 activity also increases during the acute phase response (6 -8, 16). Despite a lack of understanding for the physiologic function of the circulatory sialyltransferase, there have been numerous reports strongly correlating serum ST6Gal-1 with pathologic conditions, such as cancer (17). Elevated circulatory ST6Gal-1 activity has been associated with disease severity and poorer prognosis in oral and breast cancers (18,19).…”

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confidence: 99%

Role for Hepatic and Circulatory ST6Gal-1 Sialyltransferase in Regulating Myelopoiesis

Jones

Nasirikenari

et al. 2010

Journal of Biological Chemistry

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Recent findings have established a role for the ST6Gal-1 sialyltransferase in modulating inflammatory cell production during Th1 and Th2 responses. ST6Gal-1 synthesizes the Sia(␣2,6) to Gal(␤1,4)GlcNAc linkage on glycoproteins on cell surfaces and in systemic circulation. Engagement of P1, one of six promoter/regulatory regions driving murine ST6Gal-1 gene expression, generates the ST6Gal-1 for myelopoietic regulation. P1 utilization, however, is restricted to the liver and silent in hematopoietic cells. We considered the possibility that myelopoiesis is responsive to the sialylation of liver-derived circulatory glycoproteins, such that reduced ␣2,6-sialylation results in elevated myelopoiesis. However, 2-dimensional differential in gel electrophoresis (2D-DIGE) analysis disclosed only minimal alterations in the sialylation of sera glycoproteins of ST6Gal-1-deficient mice when compared with wild-type controls, either at baseline or during an acute phase response when the demand for sialylation is greatest. Furthermore, sera from ST6Gal-1-deficient animals did not enhance myelopoietic activity in ex vivo colony formation assays. Whereas there was only minimal consequence to the ␣2,6-sialylation of circulatory glycoproteins, ablation of the P1 promoter did result in strikingly depressed levels of ST6Gal-1 released into systemic circulation. Therefore, we considered the alternative possibility that myelopoiesis may be regulated not by the hepatic sialyl glycoproteins, but by the ST6Gal-1 that was released directly into circulation. Supporting this, ex vivo colony formation was notably attenuated upon introduction of physiologic levels of ST6Gal-1 into the culture medium. Our data support the idea that circulatory ST6Gal-1, mostly of hepatic origin, limits myelopoiesis by a mechanism independent of hepatic sialylation of serum glycoproteins.␣2,6-Sialic acid modification is a common feature of glycoproteins in systemic circulation, particularly those glycoproteins originating from the liver. The ␣2,6 attachment of sialic acid to Gal(␤1,4)GlcNAc termini of glycoproteins is mediated by the sialyltransferase ST6Gal-1. Mutant mice unable to express ST6Gal-1 are essentially devoid of ␣2,6-sialyl modifications, as evidenced by the lack of binding to the Sambucus nigra lectin (SNA) 2 that specifically recognizes these structures (1). Hepatic expression of ST6Gal-1 is principally driven by P1 (2, 3), one of six independently operative promoter regions regulating transcription of the ST6Gal-1 gene (4). Another promoter, P3, is responsible for low-level ST6Gal-1 expression in the liver (5). Increased expression of liver ST6Gal-1, mediated by the P1 promoter, has long been recognized to be an integral part of the acute phase response (APR) (6 -8), and it was generally believed that elevation of ST6Gal-1 was necessary to address the increased demand for sialylation of the acute phase proteins. The Siat1⌬P1 mouse, with a specific inactivation of P1 without compromising ST6Gal-1 gene expression from the remaining promoters, was ...

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confidence: 99%

Role for Hepatic and Circulatory ST6Gal-1 Sialyltransferase in Regulating Myelopoiesis

Jones

Nasirikenari

et al. 2010

Journal of Biological Chemistry

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“…Although altered glycoconjugates correlate with an increased propensity to liver metastasis in animal models [30], we failed to find a correlation with AJCC tumor classification. In some studies, α(2,6)-sialylation is negatively correlated with a good clinical outcome in CRC patients [18, 20, 28]. But in those studies the most widely used tool for the investigation of the sialyl-α(2,6)-linkage was Sambucus nigra agglutinin and this lectin not only recognizes the CDw75 antigen, but also recognizes the sTn epitope, another glycan structure highly expressed in colon cancer tissues that has also been related to patient survival [31].…”

Section: Discussionmentioning

confidence: 99%

“…In any case, a large percentage of primary and metastatic gastrointestinal carcinomas show increased activity with anti-CDw75 antibodies [32, 33] and elevation of ST6Gal I mRNA in colorectal tissues [34, 35] and in colorectal cancer cells [20] have also been related to the metastasis process. One possible explanation is connected with the nonadhesiveness of the cells [28], because it has been proposed that a process of selection for metastatic cells by hypersialylation of specific tumor cell surface glycoconjugates would promote the release of single cells from the primary tumor mass [20, 30].…”

Section: Discussionmentioning

confidence: 99%

“…This epitope is widely distributed in CRC tissues and was detected by means of Sambucus nigra agglutinin [17,18,19,20] and has further been shown to be positively associated with an invasive phenotype in some experimental studies [6, 17, 18]. The upregulation of ST6Gal I is probably at the origin of the increased α(2,6)-sialylation of cancer cells [20], therefore, it would be very important to clarify the role of this enzyme in CRC.…”

Section: Introductionmentioning

confidence: 99%

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Elevation of ST6Gal I Activity in Malignant and Transitional Tissue in Human Colorectal Cancer

Vázquez-Martín

Gil‐Martín²,

Fernández-Briera³

2005

Oncology

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Objectives: The aim of the present study was to investigate the activity of CMP-NeuAc:Galβ(1,4)GlcNAc sialyltransferase (ST6Gal I) in colorectal cancer (CRC). Methods: ST6Gal I activity was determined in healthy, transitional and tumor tissues from the same patient using asialotransferrin and N-acetyllactosamine as acceptors. Results: ST6Gal I activities with asialotransferrin (n = 85) and N-acetyllactosamine (n = 40) as acceptors were statistically significantly enhanced in CRC tissue compared with healthy mucosa from the same patient (p = 0.001). Using transitional tissue (n = 27), enhancement versus healthy tissue was observed (p < 0.05). A positive correlation was found between ST6Gal I activity with N-acetyllactosamine and asialotransferrin in healthy (n = 32), tumorous (n = 32) and transitional tissue (n = 27), supporting the fact that the same enzyme was detected using both acceptors. Furthermore, we studied the relationship between some patients’ clinicopathological features and ST6Gal I activity. Although the differences were not statistically significant, the levels of ST6Gal I activity in tumorous and transitional tissues varied with the histological grade of the tumor; however, we failed to find a correlation with the AJCC tumor classification. Conclusions: This work reports enhanced ST6Gal I activity in tumor and transitional tissues from CRC patients. However, our overall results suggest that ST6Gal I activity is not indicative of the patient’s outcome.

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“…4) Fifteen or more human ST cDNAs have also been cloned and characterized based on their substrate specificities: ST3Gal I to V, ST6Gal I, ST3GalNAc I to VI, and ST8Sia I to V. Each of the ST genes is differentially expressed in a tissue-, cell type-, and stagespecific manner. 5) It has previously been reported that expression of FUT IV mRNA is moderately and ST3Gal I mRNA prominently increased in human colorectal cancer tissues 6,7) and that FUT III, FUT VI and ST3Gal IV are the most abundantly expressed and FUT IV, ST3Gal II, ST3Gal I and ST6Gal I are increased in colorectal carcinoma. 8) These reports have indicated that FUT III and IV and ST3Gal I and IV are mainly responsible for the biosynthesis of distal glycans such as Lewis-type antigens.…”

mentioning

confidence: 97%

NF.KAPPA.B-p65 Dependent Transcriptional Regulation of Glycosyltransferases in Human Colon Adenocarcinoma HT-29 by Stimulation with Tumor Necrosis Factor .ALPHA.

Higai

Ishihara

Matsumoto

2006

Biological & Pharmaceutical Bulletin

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Untitled

Cited by 247 publications

References 140 publications

Role for Hepatic and Circulatory ST6Gal-1 Sialyltransferase in Regulating Myelopoiesis

Role for Hepatic and Circulatory ST6Gal-1 Sialyltransferase in Regulating Myelopoiesis

Elevation of ST6Gal I Activity in Malignant and Transitional Tissue in Human Colorectal Cancer

NF.KAPPA.B-p65 Dependent Transcriptional Regulation of Glycosyltransferases in Human Colon Adenocarcinoma HT-29 by Stimulation with Tumor Necrosis Factor .ALPHA.

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