title: Accumulation of unusual gangliosides G(Q3) and G(P3) in breast cancer cells expressing the G(D3) synthase.
abstract: 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, SIAT 8a) is the key enzyme controlling the biosynthesis of b- and c-series gangliosides. ST8Sia I is expressed at early developmental stages whereas in adult human tissues, ST8Sia I transcripts are essentially detected in brain. ST8Sia I together with b- and c-series gangliosides are also over-expressed in neuroectoderm-derived malignant tumors such as melanoma, glioblastoma, neuroblastoma and in estrogen receptor (ER) negative breast cancer, where they play a role in cell proliferation, migration, adhesion and angiogenesis. We have stably expressed ST8Sia I in MCF-7 breast cancer cells and analyzed the glycosphingolipid composition of wild type (WT) and GD3S+ clones. As shown by mass spectrometry, MCF-7 expressed a complex pattern of neutral and sialylated glycosphingolipids from globo- and ganglio-series. WT MCF-7 cells exhibited classical monosialylated gangliosides including G(M3), G(M2), and G(M1a). In parallel, the expression of ST8Sia I in MCF-7 GD3S+ clones resulted in a dramatic change in ganglioside composition, with the expression of b- and c-series gangliosides as well as unusual tetra- and pentasialylated lactosylceramide derivatives G(Q3) (II(3)Neu5Ac(4)-Gg(2)Cer) and G(P3) (II(3)Neu5Ac(5)-Gg(2)Cer). This indicates that ST8Sia I is able to act as an oligosialyltransferase in a cellular context.
authors.affiliation: Structural and Functional Glycobiology Unit, UMR CNRS 8576, University of Sciences and Technologies of Lille, 59655 Villeneuve d'Ascq, France. agata.steenackers@hotmail.fr
authors.forename: Agata
authors.initials: A
authors.lastname: Steenackers
authors.forename: Jorick
authors.initials: J
authors.lastname: Vanbeselaere
authors.forename: Aurélie
authors.initials: A
authors.lastname: Cazet
authors.forename: Marie
authors.initials: M
authors.lastname: Bobowski
authors.forename: Yoann
authors.initials: Y
authors.lastname: Rombouts
authors.forename: Florent
authors.initials: F
authors.lastname: Colomb
authors.forename: Xuefen
authors.initials: X
authors.lastname: Le Bourhis
authors.forename: Yann
authors.initials: Y
authors.lastname: Guérardel
authors.forename: Philippe
authors.initials: P
authors.lastname: Delannoy
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005732:Gangliosides / Q000096:biosynthesis / Q000378:metabolism*; D015870:Gene Expression; D006028:Glycosphingolipids / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008745:Methylation; D012799:Sialyltransferases / Q000235:genetics* / Q000378:metabolism*
chemical_list: D005732:Gangliosides; D006028:Glycosphingolipids; D012799:Sialyltransferases; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase