Direct interaction between surface β1,4-galactosyltransferase 1 and epidermal growth factor receptor (EGFR) inhibits EGFR activation in hepatocellular carcinoma.
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| Abstract |
Our previous studies showed that cell surface β1,4-galactosyltransferase 1 (β1,4GT1) negatively regulated cell survival through inhibition and modulation of the epidermal growth factor receptor (EGFR) signaling pathway in human hepatocellular carcinoma (HCC) SMMC-7721 cells. However, the underlying mechanism remains unclear. Here we demonstrated that β1,4-galactosyltransferase 1 (β1,4GT1) interacted with EGFR in vitro by GST pull-down analysis. Furthermore, we demonstrated that β1,4GT1 bound to EGFR in vivo by co-immunoprecipitation and determined the co-localization of β1,4GT1 and EGFR on the cell surface via confocal laser scanning microscopy analysis. Finally, using (125)I-EGF binding experiments and Western blot analysis, we found that overexpression of β1,4GT1 inhibited (125)I-EGF binding to EGFR, and consequently reduced the levels of EGFR dimerization and phosphorylation. In contrast, RNAi-mediated knockdown of β1,4GT1 increased the levels of EGFR dimerization and phosphorylation. These data suggest that cell surface β1,4GT1 interacts with EGFR and inhibits EGFR activation.
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| Authors | Wenqing Tang, Shuqiang Weng, Si Zhang, Weibing Wu, Ling Dong, Xizhong Shen, Songwen Zhang, Jianxin Gu, Ruyi Xue |
| Journal | Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 434 Issue 3 Pg. 449-54 (May 10 2013) ISSN: 1090-2104 [Electronic] United States |
| PMID | 23583406 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2013 Elsevier Inc. All rights reserved. |
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