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作 者:FeiGENG BiZhiSHI YunFengYUAN XingZhongWU
机构地区:[1]DepartmentofBiochemistryandMolecularBiology,FudanUniversityMedicalCenter,Shanghai200032,China [2]DepartmentofThoracicSurgery,ZhongshanHospital,FudanUniversity,Shanghai200032,China
出 处:《Cell Research》2004年第5期423-433,共11页细胞研究(英文版)
基 金:supported by the National Nature Science Foundation of China(No.30070183,No.30470398);Key Subject Foundation of Shanghai Municipal Education Committee(No.B9808010).
摘 要: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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