Glycosyltransferases involved in the synthesis of MUC-associated metastasis-promoting selectin ligands.
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.
['Chachadi|Vishwanath B|VB|', 'Bhat|Ganapati|G|', 'Cheng|Pi-Wan|PW|']
D018395:CA-19-9 Antigen D002448:Cell Adhesion D045744:Cell Line, Tumor D002465:Cell Movement D004847:Epithelial Cells D005700:Galactosyltransferases D006801:Humans D008562:Membrane Glycoproteins D009077:Mucins D009844:Oligosaccharides D000080506:Sialyl Lewis X Antigen
glycosyltransferases metastasis cell adhesion glycosylation lung cancer sialyl Lewis antigens