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

• Published in: Molecular biology reports 2011-03, Vol.38 (3), p.1541
• Main Authors: Shen, Li, Liu, Zhenhua, Tu, Youbin, Xu, Lan, Sun, Xiaoya, Wu, Shiliang
• Format: Article
• Language: English
• Subjects: Cancer; Gastrointestinal diseases; Gene expression; Glycoproteins; Molecular biology; Proteins
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-010-0262-4

β-1,3-N-acetylglucosaminyltransferase-8(β3Gn-T8) catalyzes the transfer of GlcNAc to the non-reducing terminus of the Galβ1-4GlcNAc 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 β3Gn-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 β3Gn-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 β3Gn-T8 siRNA transfected cells. Furthermore, cells overexpressing β3Gn-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 β3Gn-T8 and MMP-2 may have related signal pathway. In summary, our results reveal a new mechanism by which β3Gn-T8 can regulate MMP-2 and TIMP-2. We suggest that β3Gn-T8 can be used as a novel therapeutic target for human gastric treatment.[PUBLICATION ABSTRACT]