Philippe Delannoy

University of Lille - Sciences and Technologies · Structural and Functional Glycobiology Unit - UGSF - UMR CNRS 8576

GD3 synthase controls the biosynthesis of complex gangliosides, bearing two or more sialic acid residues. Disialylated gangliosides GD3 and GD2 are tumor-associated carbohydrate antigens (TACA) in neuro–ectoderm-derived cancers, and are directly involved in cell malignant properties, i.e., migration, invasion, stemness, and epithelial–mesenchymal t...

Gangliosides are acidic glycosphingolipids substituted by one or more sialic acid residues. The expression of complex gangliosides from b- and c-series, which are characterized by the presence of at least two sialic acid residues linked to lactosylceramide, is limited to the nervous system in healthy adults. However, complex gangliosides are re-exp...

Mucin-type O-glycosylation is one of the most important modifications of epithelial cell membrane glycoproteins and plays important roles in a variety of biological functions in-cluding cell interactions, bacterial adhesion, immunogenicity and signaling. Alterations of O-glycosylation are observed in inflammatory diseases due to the modulation of g...

The O-acetylated form of GD2, almost exclusively expressed in cancerous tissues, is considered to be a promising therapeutic target for neuroectoderm-derived tumors, especially for breast cancer. Our recent data have shown that 9-O-acetylated GD2 (9-OAcGD2) is the major O-acetylated ganglioside species in breast cancer cells. In 2015, Baumann et al...

Aberrant expression of glycosphingolipids is a hallmark of cancer cells and is associated with their malignant properties. Disialylated gangliosides GD2 and GD3 are considered as markers of neuroectoderm origin in tumors, whereas fucosyl-GM1 is expressed in very few normal tissues but overexpressed in a variety of cancers, especially in small cell...

La glycosylation est l’une des modifications essentielles des protéines et des lipides. Elle s’effectue principalement dans le réticulum endoplasmique et l’appareil de Golgi et fait appel à une machinerie moléculaire spécifique, associant plusieurs centaines de glycosyltransférases, de glycosidases, de transporteurs et de protéines régulatrices. De...

O-acetylation of sialic acid residues is one of the main modifications of gangliosides, and modulates ganglioside functions. O-acetylation of gangliosides is dependent on sialyl-O-acetyltransferases and sialyl-O-acetyl-esterase activities. CAS1 Domain-Containing Protein 1 (CASD1) is the only human sialyl-O-acetyltransferases (SOAT) described until...

Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in numbe...

The expression and biological functions of oncofetal markers GD2 and GD3 were extensively studied in neuroectoderm-derived cancers in order to characterize their potential as therapeutic targets. Using immunological approaches, we previously identified GD3, GD2, and OAcGD2 expression in breast cancer (BC) cell lines. However, antibodies specific fo...

Gangliosides, the glycosphingolipids carrying one or several sialic acid residues, are mostly localized at the plasma membrane in lipid raft domains and implicated in many cellular signaling pathways mostly by interacting with tyrosine kinase receptors. Gangliosides are divided into four series according to the number of sialic acid residues, which...

Mainly restricted to the nervous system in healthy adults, complex gangliosides such as GD3 and GD2 have been shown to be involved in aggressiveness and metastasis of neuro-ectoderm derived tumors such as melanoma and neuroblastoma. Interestingly, O-acetylated forms of GD2, not expressed in human peripheral nerve fibers, are highly expressed in GD2...

The mammalian mono-↵2,8-sialyltransferase ST8Sia VI has been shown to catalyze the transfer of a unique sialic acid residues onto core 1 O-glycans leading to the formation of di-sialylated O-glycosylproteins and to a lesser extent to diSia motifs onto glycolipids like GD1a. Previous studies also reported the identification of an orthologue of the S...

Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in a num...

Gangliosides are glycosphingolipids concentrated in glycolipid-enriched membrane microdomains. Mainly restricted to the nervous system in healthy adult, complex gangliosides such as GD3 and GD2 have been shown to be involved in aggressiveness and metastasis of neuro-ectoderm derived tumors such as melanoma and neuroblastoma. GD3 synthase (GD3S), th...

At the outer leaflet of the plasma membrane, gangliosides are found with other glycosphingolipids, phospholipids, and cholesterol in glycolipid-enriched microdomains, in which they interact with signaling molecules including receptor tyrosine kinases and signal transducers. The role of gangliosides in the regulation of signal transduction has been...

Gangliosides are acidic glycosphingolipids containing one or more sialic acid residues. They are essential compounds at the outer leaflet of the plasma membrane where they interact with phospholipids, cholesterol and transmembrane proteins, forming lipid rafts. They are involved in cell adhesion, proliferation and recognition processes, as well as...

The occurrence and biological importance of sialic acid (Sia) and its metabolic enzymes in insect have been studied using Drosophila melanogaster The most prominent feature of D. melanogaster CMP-Sia synthetase (DmCSS) is its Golgi-localization, contrasted with nuclear localization of vertebrate CSSs. However, it remains unclear if the Golgi-locali...

The Thomsen Friedenreich (TF) carbohydrate antigens are a group of short O-glycans overexpressed on most carcinomas that have been correlated with cancer progression and poor prognosis. Usually associated with immunosuppressive tumor environment, there is a number of potential immunotherapeutics against TF antigens have been developed, which compri...

Glycosylation is one of the most important modifications of proteins and lipids, and cell surface glycoconjugates are thought to play important roles in a variety of biological functions including cell-cell and cell-substrate interactions, bacterial adhesion, cell immunogenicity and cell signaling. Alterations of glycosylation are observed in numbe...

We have previously shown that TNF induced the up-regulation of the sialyltransferase gene ST3GAL4 BX transcript through mitogen- and stress-activated kinase 1/2 (MSK1/2), extracellular-signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. This up-regulation resulted in sialyl-Lewis(x) (sLe(x)) over-expres...

The ST6GALNAC5 gene that encodes an α2,6-sialyltransferase involved in the biosynthesis of α-series gangliosides, was previously identified as one of the genes that mediate breast cancer metastasis to the brain. We have shown that the expression of ST6GALNAC5 in MDA-MB-231 breast cancer cells resulted in the expression of GD1α ganglioside at the ce...

Distant metastases account for the majority of cancer-related deaths in breast cancer. The rate and site of metastasis differ between estrogen receptor (ER)-negative and ER-positive tumours, and metastatic fate can be very diverse even within the ER-negative group. Characterisation of new pro-metastatic markers may help to identify patients with hi...

Around 7-17% of metastatic breast cancer patients will develop brain metastases, associated with a poor prognosis. To reach the brain parenchyma, cancer cells need to cross the highly restrictive endothelium of the Blood-Brain Barrier (BBB). As treatments for brain metastases are mostly inefficient, preventing cancer cells to reach the brain could...

The carbohydrate antigens Tn and sialyl-Tn (STn) are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited succe...

Gangliosides are essential compounds of the plasma membrane involved in cell adhesion, proliferation, and recognition processes, as well as in the modulation of signal transduction pathways. These functions are mainly supported by the glycan moiety, and changes in the structure of gangliosides occur under pathological conditions including cancers....

α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b, to form GD1α and is considered as t...

Dengue fever (DF) is the most prevalent arthropod-borne viral disease which affects humans. DF is caused by the four dengue virus (DENV) serotypes, which are transmitted to the host by the mosquito Aedes aegypti that has key roles in DENV infection, replication, and viral transmission (vector competence). Mosquito saliva also plays an important rol...

Supplementary Figure 1: CLUSTALW analysis of Aedes aegypti CSAS. Supplementary Figure 2: MAA Lectin in the midguts of Aedes aegypti and the SGs of Aedes aegypti and Drosophila melanogaster. Supplementary Figure 3: DENV interaction with Aedes aegypti midgut. Supplementary Figure 4: Mass analysis of ions obtained with MALDI–ToF and the equivalent pep...

Sialic acids are nine-carbon acidic monosaccharides found in terminal position of glycan chains. The sialylation of cell surface glycoconjugates is frequently altered in cancers, resulting in the expression of sialylated tumor-associated carbohydrate antigens that are specific markers for this disease. Because sialylated glycans are involved in man...

Complex interplays between proteins, lipids and carbohydrates can alter the phenotype and are suggested to have a crucial role in tumour metastasis. Our previous studies indicated that a complex of the glycosphingolipids, asialo-GM1, which lacks a2,3-linked sialic acid, and a2b1 integrin receptors is responsible for the metastatic behaviour of C4-2...

Mucins are high molecular weight glycoproteins characterized by highly O-glycosylated tandem repeat domains. Mucin-type O-glycans exhibit a variety of terminal sequences including histo-blood group antigens that serve as counter receptors and participate in the adhesion and clearance of numerous bacteria including pathogens. In parallel, the pathol...

The CMP-sialic acid: sialylα2-3Galβ1-4Glcβ1-O-Cer α2,8-sialyltransferase (ST8Sia I) is the key enzyme for the biosynthesis of b-series gangliosides. ST8Sia I catalyses the transfer of a sialic acid residue from CMP-sialic acid onto GM3 (Neu5Acα2-3Galβ1-4Glcβ1-O-Cer) to form GD3 (Neu5Acα2-8Neu5Acα2-3Galβ1-4Glcβ1-O-Cer). The product GD3 can be conver...

The CMP-sialic acid: sialylα2-3Galβ1-4Glcβ1-O-Cer α2,8-sialyltransferase (ST8Sia I) is the key enzyme for the biosynthesis of b-series gangliosides. ST8Sia I catalyses the transfer of a sialic acid residue from CMP-sialic acid onto GM3 (Neu5Acα2-3Galβ1-4Glcβ1-O-Cer) to form GD3 (Neu5Acα2-8Neu5Acα2-3Galβ1-4Glcβ1-O-Cer). The product GD3 can be conver...

Gangliosides, the glycosphingolipids carrying one or several sialic acid residues, are located on the outer leaflet of the plasma membrane in glycolipid-enriched microdomains, where they interact with molecules of signal transduction pathways including receptors tyrosine kinases (RTKs). The role of gangliosides in the regulation of signal transduct...

We have previously shown that the pro-inflammatory cytokine TNF (tumour necrosis factor) could drive sLex (sialyl-Lewisx) biosynthesis through the up-regulation of the BX transcript isoform of ST3GAL4 sialyltransferase gene in lung epithelial cells and human bronchial mucosa. Here, we show that the TNF-induced up-regulation of ST3GAL4 BX transcript...

Enhanced metabolism of fucose through fucosidase overexpression is a signature of some cancer types, thus suggesting that fucosidase-targetted ligands could play the role of drug-delivery vectors. Herein, we describe the synthesis of a new series of pyrrolidine-ferrocene conjugates, consisting of a L-fuco-configured dihydroxypyrrolidine as the fuco...

Sialyl-Tn is a carbohydrate antigen overexpressed in several epithelial cancers, including breast cancer, and usually associated with poor prognosis. Sialyl-Tn is synthesized by a CMP-Neu5Ac:GalNAcalpha2,6-sialyltransferase: CMP-Neu5Ac: R-GalNAcalpha1-O-Ser/Thr alpha2,6-sialyltransferase (EC 2.4.99.3) (ST6GalNAc I), which transfers a sialic acid re...

Distant metastasis account for about 90 % of cancer associated deaths, and yet the oncology field is cruelly lacking tools to accurately predict and/or prevent metastasis. Distant metastasis occurs when circulating tumor cells interact with the endothelium of distant organs and extravasate from the blood vessel into the surrounding tissue. Selectin...

The CMP–sialic acid: sialylα2-3Galβ1-4Glcβ1-O-Cer α2,8-sialyltransferase (ST8Sia I) is the key enzyme for the biosynthesis of b-series gangliosides. ST8Sia I catalyses the transfer of a sialic acid residue from CMP–sialic acid onto GM3 (Neu5Acα2-3Galβ1-4Glcβ1-O-Cer) to form GD3 (Neu5Acα2-8Neu5Acα2-3Galβ1-4Glcβ1-O-Cer). The product GD3 can be conver...

Recent data have underlined a possible role of GD3 synthase (GD3S) and complex gangliosides in Estrogen Receptor (ER) negative breast cancer progression. Here, we describe the main transcript of the GD3S coding gene ST8SIA1 expressed in breast tumors. We characterized the corresponding core promoter in Hs578T breast cancer cells and showed that est...

Sialyl-Tn antigen (STn) is a short O-glycan containing a sialic acid residue a2,6-linked to GalNAca-O-Ser/Thr. The biosynthesis of STn is mediated by a specific sialyltransferase termed ST6GalNAc I, which competes with O-glycans elongating glycosyltransferases and prevents cancer cells from exhibiting longer O-glycans. While weakly expressed by fet...

Bronchial mucins from severely infected patients suffering from lung diseases such as chronic bronchitis or cystic fibrosis exhibit increased amounts of sialyl-Lewis x (NeuAca2-3Galb1-4[Fuca1-3]GlcNAc-R, sLe x) glycan structures. In cystic fibrosis, sLe x and its sulfated form 6-sulfo-sialyl-Lewis x (NeuAca2-3Galb1-4 [Fuca1-3](HO 3 S-6)GlcNAc-R, 6-...

Glycosphingolipids from the ganglio-series are usually classified in four series according to the presence of 0 to 3 sialic acid residues linked to lactosylceramide. The transfer of sialic acid is catalyzed in the Golgi apparatus by specific sialyltransferases that show high specificity toward glycolipid substrates. ST8Sia I (EC 2.4.99.8, SAT-II, S...

We prepared a series of new iminosugar-ferrocene hybrids displaying potent inhibition of fucosidase (bovine kidney) and inactivation of MDA-MB-231 breast cancer cells proliferation at low micromolar concentrations. The synthetic route brought to light an unprecedented isomerisation of a 2-ethanalylpyrrolidine.

Bronchial mucins from severely infected patients suffering from lung diseases such as chronic bronchitis or cystic fibrosis exhibit increased amounts of sialyl-Lewis(x) (NeuAcα2-3Galβ1-4[Fucα1-3]GlcNAc-R, sLe(x)) glycan structures. In cystic fibrosis, sLe(x) and its sulfated form 6-sulfo-sialyl-Lewis(x) (NeuAcα2-3Galβ1-4[Fucα1-3](HO(3)S-6)GlcNAc-R,...

We have recently established and characterized cellular clones deriving from MDA-MB-231 breast cancer cells that express the human G(D3) synthase (GD3S), the enzyme that controls the biosynthesis of b- and c-series gangliosides. The GD3S positive clones show a proliferative phenotype in the absence of serum or growth factors and an increased tumor...

Abnormally elevated levels of sialylated tumor associated carbohydrate antigens are frequently described at the surface of cancer cells and/or secreted in biological fluids. It is now well established that this over-expression may result from deregulation in sialyltransferases enzymatic activity involved in their biosynthesis, but the precise molec...

Glycosylation changes that occur in cancer often lead to the expression of Tumor Associated Carbohydrate Antigens that are usually associated with a poor prognosis and a reduced overall survival. Within these carbohydrate antigens, complex gangliosides from b- and c-series, usually restricted to the nervous system in adult, can be re-expressed in n...

The animal sialyltransferases (ST) superfamily comprises 4 ST families (ST3Gal, ST6Gal, ST6GalNAc and ST8Sia) and 20 ST subfamilies in higher vertebrates that catalyze the transfer of sialic acid residues. We have recently identified the 4 families in invertebrate genome suggesting ancient occurrence and divergent evolution of STs [1]. ST6Gal-I and...

The Sda/Cad antigen (GalNAcβ1-4[Neu5Aca2-3]Galß1-4GlcNAc), is an onco-developmentally regulated antigen expressed on glycolipids and glycoproteins in the human gastrointestinal (GI) mucosa with an increasing gradient from the ileum to the colon. On the other hand, the sLe x antigen (Neu5Acα2-3Galβ1-4[Fucα1-3]GlcNAc) is not or very weakly expressed...

B- and c-series of gangliosides are over-expressed in neuro-ectoderm-related cancers, including breast cancer. It has been shown that GD3 ganglioside is over-expressed in about 50% of invasive ductal breast carcinoma and the GD3 synthase (GD3S) gene displays higher expression among estrogen receptor (ER) negative breast tumors. We previously showed...

Effect of transcription factors over-expression on fut8 P1 minimal promoter activity. Bioinformatics analysis identified consensus binding sites for PRDM1, IRF3, PAX5, MZF1 and KLF15 putative repressors in the T1 transcript minimal promoter sequence. Human coding sequence of PRDM1, IRF3 and MZF1 were cloned into the pcDNA3.1 expression vector using...

The rat hybridoma cell line YB2/0 appears a good candidate for the large-scale production of low fucose recombinant mAbs due to its lower expression of fut8 gene than other commonly used rodent cell lines. However, important variations of the fucose content of recombinant mAbs are observed in production culture conditions. To improve our knowledge...

Sialyltransferases are key enzymes in the biosynthesis of sialoglycoconjugates that catalyze the transfer of sialic residue from its activated form to an oligosaccharidic acceptor. β-Galactoside α2,6-sialyltransferases ST6Gal I and ST6Gal II are the two unique members of the ST6Gal family described in higher vertebrates. The availability of genome...

Sialyltransferases (STs) represent an important group of enzymes that transfer N-acetylneuraminic acid (Neu5Ac) from cytidine monophosphate-Neu5Ac to various acceptor substrates. In higher animals, sialylated oligosaccharide structures play crucial roles in many biological processes but also in diseases, notably in microbial infection and cancer. C...