Nie Huan, Liu Xia, Zhang Yubao, Li Tingting, Zhan Chao, Huo Wenjuan, He Anshun, Yao Yuanfei, Jin Yu, Qu Youpeng, Sun Xue-Long, Li Yu
School of Life Science and Technology, Harbin Institute of Technology, Heilongjiang, China.
School of Basic Medical Sciences, Mudanjiang Medical University, Heilongjiang, China.
Sci Rep. 2015 Nov 5;5:16007. doi: 10.1038/srep16007.
Glycosylation alterations of cell surface proteins are often observed during the progression of malignancies. The specific cell surface N-glycans were profiled in hepatocellular carcinoma (HCC) with clinical tissues (88 tumor and adjacent normal tissues) and the corresponding serum samples of HCC patients. The level of core-α-1,6-fucosylated triantennary glycan (NA3Fb) increased both on the cell surface and in the serum samples of HCC patients (p < 0.01). Additionally, the change of NA3Fb was not influenced by Hepatitis B virus (HBV)and cirrhosis. Furthermore, the mRNA and protein expression of N-acetylglucosaminyltransferase IVa (GnT-IVa), which was related to the synthesis of the NA3Fb, was substantially increased in HCC tissues. Knockdown of GnT-IVa leads to a decreased level of NA3Fb and decreased ability of invasion and migration in HCC cells. NA3Fb can be regarded as a specific cell surface N-glycan of HCC. The high expression of GnT-IVa is the cause of the abnormal increase of NA3Fb on the HCC cell surface, which regulates cell migration. This study demonstrated the specific N-glycans of the cell surface and the mechanisms of altered glycoform related with HCC. These findings lead to better understanding of the function of glycan and glycosyltransferase in the tumorigenesis, progression and metastasis of HCC.
在恶性肿瘤进展过程中，常观察到细胞表面蛋白的糖基化改变。利用临床组织（88例肿瘤组织和相邻正常组织）以及肝癌（HCC）患者的相应血清样本，对肝癌细胞表面特定的N-聚糖进行了分析。核心α-1,6-岩藻糖基化三天线聚糖（NA3Fb）在肝癌患者的细胞表面和血清样本中的水平均升高（p < 0.01）。此外，NA3Fb的变化不受乙型肝炎病毒（HBV）和肝硬化的影响。此外，与NA3Fb合成相关的N-乙酰葡糖胺基转移酶IVa（GnT-IVa）在肝癌组织中的mRNA和蛋白表达显著增加。敲低GnT-IVa会导致肝癌细胞中NA3Fb水平降低以及侵袭和迁移能力下降。NA3Fb可被视为肝癌特异性的细胞表面N-聚糖。GnT-IVa的高表达是肝癌细胞表面NA3Fb异常增加的原因，其调节细胞迁移。本研究揭示了肝癌细胞表面特异性N-聚糖以及与肝癌相关的糖型改变机制。这些发现有助于更好地理解聚糖和糖基转移酶在肝癌发生、发展和转移中的作用。
