ARTICLES

Cell Research (2004); 14(5):423-433

The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications

Fei GENG1, Bi Zhi SHI 1, Yun Feng YUAN2, Xing Zhong WU1*

1Department of Biochemistry and Molecular Biology, Fudan University Medical Center, Shanghai 200032, China
2 Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China

Received, Feb 4, 2004     Revised, Jun 6, 2004     Accepted, Jun 18, 2004
Correspondence:
Xing Zhong WU
0086-21-54237697 (phone)
0086-21-64278329 (fax)
xz-wu@shmu.edu.cn
Abstract

It is well documented that the glycosylation of E-cadherin is correlated with cancer metastasis, but whether E-cadherin could be core fucosylated remains largely unknown. We found that E-cadherin was core fucosylated in highly metastatic lung cancer cells while absent in lowly metastatic lung cancer cells. Since ¦Á-1,6 Fucosyltransferase (¦Á-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by ¦Á-1,6 FucT targeted RNAi and transfecting ¦Á-1,6 FucT expression vector. As a result, calcium dependent cell-cell adhesion mediated by E-cadherin was strengthened with the reduction of core fucosylation on E-cadherin after RNAi and was weakened with the elevated core fucosylation on E-cadherin after ¦Á-1,6 FucT over expression. Our data indicated that ¦Á-1,6 FucT could regulate E-cadherin mediated cell adhesion and thus play an important role in cancer development and progression. Computer modeling showed that core fucosylation on E-cadherin could significantly impair three-dimensional conformation of N-glycan on E-cadherin and produce conformational asymmetry so as to suppress the function of E-cadherin. Furthermore, the relationship between the expression of core fucosylated E-cadherin and clinicopathological background of lung cancer patients was explored in lung cancer tissue of patients. It turns out to demonstrate that core fucosylated E-cadherin could serve as a promising prognostic indicator for lung cancer patients.

Keywords: Core fucosylated E-cadherin, prognosis, cancer metastasis, RNA interference, molecular modeling.



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