title: 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: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors: Zhi
authors: Z
authors: Jiang
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors: Shuijun
authors: S
authors: Hu
authors: The Fourth People's Hospital of Wuxi, The Original Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.
authors: Dong
authors: D
authors: Hua
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors: Jianlong
authors: J
authors: Ni
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors: Lan
authors: L
authors: Xu
authors: Department of Immunology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors: Yan
authors: Y
authors: Ge
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors: Yinghui
authors: Y
authors: Zhou
authors: The Fourth People's Hospital of Wuxi, The Original Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.
authors: Zhihong
authors: Z
authors: Cheng
authors: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors: Shiliang
authors: S
authors: Wu
mesh_terms: D000606:Amino Sugars / Q000378:metabolism; D051926:Basigin / Q000378:metabolism*; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D006031:Glycosylation; D006801:Humans; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D015398:Signal Transduction; D014415:Tunicamycin / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D000606:Amino Sugars; C497886:BSG protein, human; D011134:Polysaccharides; C066929:polylactosamine; D014415:Tunicamycin; D051926:Basigin; C496333:B3GNT8 protein, human; D017351:N-Acetylglucosaminyltransferases; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2