Ni Jianlong, Jiang Zhi, Shen Li, Gao Liping, Yu Meiyun, Xu Xu, Zou Shitao, Hua Dong, Wu Shiliang
Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
The Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.
Oncol Rep. 2014 Apr;31(4):1795-801. doi: 10.3892/or.2014.3042. Epub 2014 Feb 20.
Aberrant glycosylation of cell surface glycoproteins is commonly associated with the invasion and metastasis of colorectal carcinomas, which can be attributed to the upregulated expression of glycosyltransferases. Therefore, elucidation of glycosyltransferases and their substrates may improve our understanding of their roles in tumor metastasis. β-1,3-N-acetylglucosaminyltransferase-8 (β3GnT8) is a key enzyme that catalyzes the formation of poly-N-acetyllactosamine (polylactosamine) chains on β1,6-branched N-glycans in vitro, which is also involved in tumor invasion. In the present study, we analyzed the expression of β3GnT8 and its product polylactosamine in four human colorectal carcinoma cell lines (LS-174T, SW620, SW480 and LoVo) with different metastatic potential. We found that the levels of β3GnT8 and polylactosamine chains were gradually increased in the colorectal cancer cell lines in a trend from low to high metastatic potential. Notably, a significantly positive relationship between β3GnT8 expression and HG-CD147 was noted in the colorectal cancer cell lines. To further investigate their relationships, exogenous β3GnT8 was introduced into the LS-174T cells, while expression of β3GnT8 was downregulated in the LoVo cells. The overexpression of β3GnT8 in LS-174T cells increased the level of HG-CD147. Conversely, downregulation of β3GnT8 expression in LoVo cells significantly decreased the expression of HG-CD147. HG-CD147 is a major carrier of β1,6-branched polylactosamine sugars; therefore, the regulation of β3GnT8 significantly altered the β1,6-branched polylactosamine structures on CD147. Hence, we suggest that β3GnT8 plays a key role in the metastasis of colorectal cancer cells by altering the β1,6-branched polylactosamine sugars of CD147.
细胞表面糖蛋白的异常糖基化通常与结直肠癌的侵袭和转移相关，这可归因于糖基转移酶表达上调。因此，阐明糖基转移酶及其底物可能会增进我们对它们在肿瘤转移中作用的理解。β-1,3-N-乙酰葡糖胺基转移酶-8（β3GnT8）是一种关键酶，它在体外催化β1,6分支的N-聚糖上多聚N-乙酰乳糖胺链的形成，其也参与肿瘤侵袭。在本研究中，我们分析了β3GnT8及其产物多聚乳糖胺在四种具有不同转移潜能的人结直肠癌细胞系（LS-174T、SW620、SW480和LoVo）中的表达。我们发现，在结直肠癌细胞系中，β3GnT8和多聚乳糖胺链的水平随着转移潜能从低到高的趋势逐渐升高。值得注意的是，在结直肠癌细胞系中，β3GnT8表达与HG-CD147之间存在显著正相关。为了进一步研究它们之间的关系，将外源性β3GnT8导入LS-174T细胞，同时在LoVo细胞中下调β3GnT8的表达。LS-174T细胞中β3GnT8的过表达增加了HG-CD147的水平。相反，LoVo细胞中β3GnT8表达的下调显著降低了HG-CD147的表达。HG-CD147是β1,6分支的多聚乳糖胺糖的主要载体；因此，β3GnT8的调节显著改变了CD147上β1,6分支的多聚乳糖胺结构。因此，我们认为β3GnT8通过改变CD147的β1,6分支的多聚乳糖胺糖在结直肠癌细胞转移中起关键作用。
