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

Cell Research 2004年第5期14卷 423-433页

作者： Fei GeNG1, Bi Zhi SHI , Yun Feng YUAN2, Xing Zhong WU1* 1 1Department of Biochemistry and Molecular Biology, Fudan University Medical Center, Shanghai 200032, China 2Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China 1Department of Biochemistry and Molecular Biology Fudan University Medical Center Shanghai 200032 China 1Department of Biochemistry and Molecular Biology Fudan University Medical Center Shanghai 200032 China 2Department of Thoracic Surgery Zhongshan Hospital Fudan University Shanghai 200032 China 1Department of Biochemistry and Molecular Biology Fudan University Medical Center Shanghai 200032 China

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 α-1,6 Fucosyltransferase (α-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on e-cadherin by α-1,6 FucT targeted RNAi and transfecting α-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 α-1,6 FucT over expression. Our data indicated that α-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 asym- metry 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.

关键词： core fucosylated e-cadherin prognosis cancer metastasis RNA interference molecular modeling.

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