Jiang Zhi, Hu Shuijun, Hua Dong, Ni Jianlong, Xu Lan, Ge Yan, Zhou Yinghui, Cheng Zhihong, Wu Shiliang
Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
The Fourth People's Hospital of Wuxi, The Original Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.
Oncol Rep. 2014 Sep;32(3):1156-62. doi: 10.3892/or.2014.3280. Epub 2014 Jun 23.
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.
相关糖基转移酶的异常糖基化在癌症进展中起重要作用。本研究聚焦于β-1,3-N-乙酰葡糖胺基转移酶-8（β3GnT8）通过调控癌细胞中CD147信号转导通路来调节MMP-2表达的能力。β3GnT8催化并特异性地在β1-6分支的四天线N-聚糖上延伸多乳糖胺链。CD147是肿瘤细胞上β1-6分支多乳糖胺糖的主要载体，且CD147的高糖型（HG-CD147）诱导基质金属蛋白酶（MMP）产生。在本研究中，我们分析了6种癌细胞系（MCF-7、M231、LN229、U87、SGC-7901和U251）中β3GnT8 mRNA的表达。我们发现LN229、SGC-7901和U251细胞系中的β3GnT8表达高于其他细胞系。因此，我们建立了源自LN229和SGC-7901细胞系的β3GnT8敲低细胞系，以检测多乳糖胺和CD147 N-糖基化水平。此外，衣霉素被广泛用作N-连接糖基化的抑制剂。因此，使用不同浓度的衣霉素处理细胞，以研究其对CD147 N-糖基化和MMP-2表达的影响。总之，我们发现β3GnT8调节CD147上的N-聚糖水平，且CD147的N-糖基化对MMP-2表达有重要影响。我们的研究结果表明，β3GnT8通过改变CD147的N-聚糖结构影响MMP-2的信号转导通路。
