The expression of core fucosylated E-cadherin in cancer cells and lung cancer patients: prognostic implications.
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 alpha-1,6 Fucosyltransferase (alpha-1,6 FucT) is known to catalyze the reaction of core fucosylation, we investigated the biological function of core fucosylation on E-cadherin by alpha-1,6 FucT targeted RNAi and transfecting alpha-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 alpha-1,6 FucT over expression. Our data indicated that alpha-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.
Geng
Fei
F
Department of Biochemistry and Molecular Biology, Fudan University Medical Center, Shanghai 200032, China.
Shi
Bi Zhi
BZ
Yuan
Yun Feng
YF
Wu
Xing Zhong
XZ
D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology; D005643:Fucose / Q000378:metabolism*; D005647:Fucosyltransferases / Q000235:genetics; D018093:Gelatinases / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D008958:Models, Molecular; D011379:Prognosis; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
D015820:Cadherins; D006023:Glycoproteins; D034741:RNA, Small Interfering; D005643:Fucose; D005647:Fucosyltransferases; C020559:Glycoprotein 6-alpha-L-fucosyltransferase; D018093:Gelatinases