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 Received, Feb 4, 2004 Revised, Jun 6, 2004 Accepted, Jun 18, 2004
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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