Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells.

Abstract

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 α1,3-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 α1,6-fucosylatransferase (FUT8) would promote EGFR dimerization and phosphorylation.

DOI: 10.1073/pnas.1107385108

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@article{Liu2011SialylationAF, title={Sialylation and fucosylation of epidermal growth factor receptor suppress its dimerization and activation in lung cancer cells.}, author={Ying-Chih Liu and Hsin-Yung Yen and Chien-Yu Chen and Chein-Hung Chen and Ping-Fu Cheng and Yi-Hsiu Juan and Chung-Hsuan Winston Chen and Kay-Hooi Khoo and Chong Yu and Pan-Chyr Yang and Tsui-Ling Hsu and Chi-Huey Wong}, journal={Proceedings of the National Academy of Sciences of the United States of America}, year={2011}, volume={108 28}, pages={11332-7} }