title: Glycosyltransferases involved in the synthesis of MUC-associated metastasis-promoting selectin ligands.
abstract: The sialyl Lewis a and x (sLe(a/x)) antigens frequently displayed on the surface of tumor cells are involved in metastasis. Their synthesis has been attributed to altered expression of selective glycosyltransferases. Identification of these glycosyltransferases and the glycoproteins that carry these carbohydrate antigens should help advance our understanding of selectin-mediated cancer metastasis. In this study, quantitative real-time polymerase chain reaction analysis coupled with in situ proximity ligation assay and small interference RNA treatment shows involvement of β3galactosyltransferase-V in the synthesis of MUC16-associated sLe(a) in H292 cells. Also, α3fucosyltransferase-V, which is absent in BEAS-2B human immortalized bronchial epithelial cells and A549 lung carcinoma cells, participates in the synthesis of MUC1-associated sLe(x) in CFT1 human immortalized bronchial epithelial cells and H292 lung carcinoma cells. Neither selectin ligand is found on MUC1 in BEAS-2B and A549 cells. Knockdown of either enzyme suppresses migration, and selectin tethering and rolling properties of H292 cells under dynamic flow as determined by wound healing and parallel plate flow chamber assays, respectively. These results provide insights into how the synthesis of mucin-associated selectin ligands and the metastatic properties of cancer cells can be regulated by selective glycosyltransferases that work on mucins. They may help develop novel anticancer drugs.
authors.affiliation: Department of Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA Department of Biochemistry and Molecular Biology, College of Medicine.
authors.forename: Vishwanath B
authors.initials: VB
authors.lastname: Chachadi
authors.affiliation: Department of Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA Department of Biochemistry and Molecular Biology, College of Medicine.
authors.forename: Ganapati
authors.initials: G
authors.lastname: Bhat
authors.affiliation: Department of Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE, USA Department of Biochemistry and Molecular Biology, College of Medicine Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, 985870 Nebraska Medical Center, Omaha, NE 68198-5870, USA pcheng@unmc.edu.
authors.forename: Pi-Wan
authors.initials: PW
authors.lastname: Cheng
mesh_terms: D018395:CA-19-9 Antigen; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism* / Q000502:physiology; D005700:Galactosyltransferases / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009077:Mucins / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen
chemical_list: D018395:CA-19-9 Antigen; D008562:Membrane Glycoproteins; D009077:Mucins; D009844:Oligosaccharides; C084882:P-selectin ligand protein; D000080506:Sialyl Lewis X Antigen; D005700:Galactosyltransferases; C419408:beta-1,4-galactosyltransferase V
keywords: cell adhesion; glycosylation; glycosyltransferases; lung cancer; metastasis; sialyl Lewis antigens