N-acetylglucosaminyltransferase IVa regulates metastatic potential of mouse hepatocarcinoma cells through glycosylation of CD147
N-acetylglucosaminyltransferase IVa regulates metastatic potential of mouse hepatocarcinoma cells through glycosylation of CD147
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N-乙酰氨基葡萄糖转移酶IVa通过CD147糖基化调节小鼠肝癌细胞的转移潜能
DOI：
10.1007/s10719-012-9414-1
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发表时间：
2012-08-01
影响因子：
3
通讯作者：
Zhang, Jianing
中科院分区：
文献类型：
--
作者：
Fan, Jianhui;Wang, Shujing;Zhang, Jianing
N-乙酰氨基葡萄糖转移酶(GnT-IV a)是催化复合N-糖链核心结构上GlcNAcβ1-4支链形成的关键酶，也是其他N-乙酰氨基葡萄糖转移酶的共同底物，如GnT-III和GnT-V。我们最近的研究表明，GnT-Iva在Hca-F细胞中的表达明显高于在Hepa1-6细胞中的表达，这两种小鼠肝癌细胞系分别具有较高的淋巴结转移潜能和无淋巴结转移潜能。为探讨GnT-Iva在肝癌转移中的作用，将外源性GnT-Iva导入Hepa1-6细胞，同时下调Hca-F细胞中GnT-Iva的表达。GnT-Iva基因在Hepa1-6细胞中的过表达增加了复合体N-糖链的触角支数，减少了体内外对分支数，从而提高了肝癌细胞的迁移和转移能力。反之，GnT-Iva在Hca-F细胞中的表达下调，显示N-糖链的四触角分支减少，迁移和转移能力显著降低。此外，我们还发现，受调控的GnT-IVa能在Hepa1-6和Hca-F细胞中转化CD147的异质性N-糖基化形式，并显著改变CD147上的触角寡糖结构。这些结果提示，GnT-IVa可能通过改变CD147的糖基化而在小鼠肝癌细胞的迁移和转移中发挥关键作用。这些发现对于阐明GnT-Iva在肝癌生长和转移过程中的重要作用具有重要意义。
N-acetylglucosaminyltransferase (GnT)-IV a is a key enzyme that catalyzes the formation of the GlcNAC beta 1-4 branch on the core structure of complex N-Glycans, which is the common substrate for other N-acetylglucosaminyltransferases, such as GnT-III and GnT-V. Our recent study indicates that the expression of GnT-IVa in Hca-F cells was much higher than that in Hepa1-6 cells, these two mouse hepatocarcinoma cell lines have high and no metastatic potential in lymph nodes respectively. To investigate the effects of GnT-IVa on the metastasis of hepatocarcinoma, exogenous GnT-IVa was introduced into Hepa1-6 cells, and on the other hand, the expression of GnT-IVa was down-regulated in Hca-F cells. The engineered overexpression of GnT-IVa in Hepa1-6 cells increased the antennary branches of complex N-glycans and reduced bisecting branches in vitro and in vivo, which leads to the increase in migration and metastatic capability of hepatocarcinoma cells. Conversely, down-regulated expression of GnT-IVa in Hca-F cells showed reduced tetra-antennary branches of N-Glycans, and significantly decreased the migration and metastatic capability. Furthermore, we found that the regulated GnT-IVa converts the heterogeneous N-glycosylated forms of CD147 in Hepa1-6 and Hca-F cells, and significantly changed the antennary oligosaccharide structures on CD147. These results suggest that GnT-IVa could be acting as a key role in migration and metastasis of mouse hepatocarcinoma cells through altering the glycosylation of CD147. These findings should be valuable in delineating the important function of GnT-IVa during the process of hepatocarcinoma growth and metastasis.