β3GnT8 plays an important role in CD147 signal transduction as an upstream modulator of MMP production in tumor cells

Abstract

Aberrant carbohydration by related glycosyltransferases plays an important role in the progression of cancer. This study focused on the ablity of β-1,3-N-acetylglucosaminyltransferase- 8 (β3GnT8) to regulate MMP-2 expression through regulation of the CD147 signal transduction pathway in cancer cells. β3GnT8 catalyzes and then extends a polylactosamine chain specifically on β1-6-branched tetraantennary N-glycans. CD147 is a major carrier of β1-6- branched polylactosamine sugars on tumor cells, and the high glycoform of CD147 (HG-CD147) induces matrix metalloproteinase (MMP) production. In the present study, we analyzed β3GnT8 mRNA expression in 6 cancer cell lines (MCF-7, M231, LN229, U87, SGC-7901 and U251). We found that β3GnT8 expression in the LN229, SGC-7901 and U251 cell lines was higher than that in the other cell lines. Therefore, we established β3GnT8-knockdown cell lines derived from the LN229 and SGC-7901 cell lines to examine the level of polylactosamine and CD147 N-glycosylation. In addition, tunicamycin is widely used as an inhibitor of N-linked glycosylation. Hence, various concentrations of tunicamycin were used to treat the cells in order to study its influence on CD147 N-glycosylation and MMP-2 expression. In conclusion, we found that β3GnT8 regulated the level of N-glycans on CD147 and that N-glycosylation of CD147 has an important effect on MMP-2 expression. Our findings suggest that β3GnT8 affects the signal transduction pathway of MMP-2 by altering the N-glycan structure of CD147.