Regulation of MMP-2 expression and activity by beta -1,3-N-acetylglucosaminyltransferase-8 in AGS gastric cancer cells

摘要

beta -1,3-N-acetylglucosaminyltransferase-8(; 2; 3Gn-T8) catalyzes the transfer of GlcNAc to the non-reducing terminus of the Gal beta 1-4GlcNAc of tetraantennary N-glycan in vitro. It has been reported to be involved in malignant tumors, but a comprehensive understanding of how the glycolsyltransferase correlates with the invasive potential of human gastric cancer is not currently available. Therefore, we investigated the ability and possible mechanism involved with beta 3Gn-T8 in modulating matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in AGS gastric cancer cells. Here, we found out that siRNA-mediated suppression of the beta 3Gn-T8 could directly reduce the MMP-2 expression and activity as observed in RT-PCR, western blot and gelatin zymography analysis. Meanwhile, TIMP-2 expression had been increased. Cell invasion assay using matrigel matrix-coated transwell inserts showed that the invasive property was greatly suppressed in beta 3Gn-T8 siRNA transfected cells. Furthermore, cells overexpressing beta 3Gn-T8 gene (when transfected with pEGFP-C1 plasmid) also expressed MMP-2 gene, but TIMP-2 expression had been inhibited. The invasive ability of these cells was also enhanced. Protein-protein interaction analysis using STRING database showed that beta 3Gn-T8 and MMP-2 may have related signal pathway. In summary, our results reveal a new mechanism by which beta 3Gn-T8 can regulate MMP-2 and TIMP-2. We suggest that beta 3Gn-T8 can be used as a novel therapeutic target for human gastric treatment.