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

Abstract

Aberrant carbohydration by related glycosyl-transferases plays an important role in the progression of cancer. This study focused on the ablity of β-1,3-N-acetyl-glucosaminyltransferase-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.

• Authors: Zhi Jiang, Shuijun Hu, Dong Hua, Jianlong Ni, Lan Xu, Yan Ge, Yinghui Zhou, Zhihong Cheng, Shiliang Wu
• Journal: Oncology reports (Oncol Rep) Vol. 32 Issue 3 Pg. 1156-62 (Sep 2014) ISSN: 1791-2431 [Electronic] Greece
• PMID: 24970053 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Sugars
• BSG protein, human
• Polysaccharides
• polylactosamine
• Tunicamycin
• Basigin
• B3GNT8 protein, human
• N-Acetylglucosaminyltransferases
• MMP2 protein, human
• Matrix Metalloproteinase 2

Topics

• Amino Sugars (metabolism)
• Basigin (metabolism)
• Cell Line, Tumor
• Gene Knockdown Techniques
• Glycosylation
• Humans
• MCF-7 Cells
• Matrix Metalloproteinase 2 (metabolism)
• N-Acetylglucosaminyltransferases (genetics, metabolism)
• Neoplasms (genetics, metabolism)
• Polysaccharides (metabolism)
• Signal Transduction
• Tunicamycin (pharmacology)
• Up-Regulation