Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells
Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells
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DOI：
10.1073/pnas.1107385108
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发表时间：
2011-07-12
影响因子：
11.1
通讯作者：
Wong, Chi-Huey
中科院分区：
文献类型：
--
作者：
Liu, Ying-Chih;Yen, Hsin-Yung;Wong, Chi-Huey
蛋白质糖基化是一个重要的翻译后过程，它调节着蛋白质的折叠和功能表达。研究表明，肿瘤细胞中的异常糖基化影响肿瘤的进展和恶性。在目前的研究中，我们使用炔基糖探针在来自同一亲本细胞系的两种不同的肺癌细胞系CL1-0和CL1-5中鉴定了唾液化蛋白，它们具有不同的侵袭性。在已鉴定的唾液化蛋白中，选择表皮生长因子受体（EGFR）来了解唾液化对其功能的影响。我们已经确定了两种细胞中EGFR聚糖序列的差异，并观察到CL1-5中EGFR的唾液化和聚焦化程度高于CL1-0。进一步的研究表明，与对照组和CL1-0细胞相比，CL1-5和A549细胞中唾液基转移酶和α 1,3-聚焦转移酶（FUT4或FUT6）的过表达会抑制EGFR二聚化和磷酸化。唾液酸酶或聚焦酶处理进一步证实了这种对EGFR二聚化的调节作用。因此，增加唾液化和聚焦化可以减弱egfr介导的肺癌细胞侵袭。然而，通过α 1,6-聚焦转移酶（FUT8）结合核心焦点会促进EGFR二聚化和磷酸化。
Protein glycosylation is an important posttranslational process, which regulates protein folding and functional expression. Studies have shown that abnormal glycosylation in tumor cells affects cancer progression and malignancy. In the current study, we have identified sialylated proteins using an alkynyl sugar probe in two different lung cancer cell lines, CL1-0 and CL1-5 with distinct invasiveness derived from the same parental cell line. Among the identified sialylated proteins, epidermal growth factor receptor (EGFR) was chosen to understand the effect of sialylation on its function. We have determined the differences in glycan sequences of EGFR in both cells and observed higher sialylation and fucosylation of EGFR in CL1-5 than in CL1-0. Further study suggested that overexpression of sialyltransferases in CL1-5 and alpha 1,3-fucosyltransferases (FUT4 or FUT6) in CL1-5 and A549 cells would suppress EGFR dimerization and phosphorylation upon EGF treatment, as compared to the control and CL1-0 cells. Such modulating effects on EGFR dimerization were further confirmed by sialidase or fucosidase treatment. Thus, increasing sialylation and fucosylation could attenuate EGFR-mediated invasion of lung cancer cells. However, incorporation of the core fucose by alpha 1,6-fucosylatransferase (FUT8) would promote EGFR dimerization and phosphorylation.