The Fucose Generating FX Enzyme and Selectin Ligands in Colorectal Cancer: A Functional Axis

摘要

The interaction of several selectin ligands with selectins is fucose-depend-ent. Fucosylation of these ligands determines their ability to interact with members of the selectin family of cell adhesion molecules. The interaction of selectins with their ligands, expressed by various leukocytes, initiates their extravasation towards inflammatory sites. Fucose biosynthesis is a multi-step event. The FX-enzyme functioning both as an epimerase and a reduct-ase, generates GDP-L fucose from GDP-D mannose. Previously we demonstrated that the FX enzyme is involved in the biosynthesis of the selectin ligands sialyl Lewis-x (sLe-x) and sialyl Lewis-a (sLe-a) in activated T or B cells and in tumor cells. In the present study we further investigated the FX-selectin ligand axis in colorectal carcinoma (CRC) cells. The results demonstrate that FX regulates also the expression levels of Lewis-x (Le-x) on CRC cells. In attempts to obtain data on the regulation of the FX-enzyme we asked if INFgamma plays any role in regulating FX expression. The results presented in this study show that INFgamma has no significant effect on FX expression by CRC cells. However INFgamma induced a significant decrease in sLe-a expression levels in such cells. These results may provide a better understanding of the functional axis played by the FX enzyme in regulating Le-x and sLe-a in colorectal cancer.