α1,3 fucosyltransferase-VII up-regulates the mRNA of α5 integrin and its biological function

After transfection of alpha 1,3fucosyltransferase (FucT)-VII cDN A into H7721 human hepatocarcinoma cells, the expression of alpha 5, but not beta 1 integrin was significantly up-regulated. This was evidenced by the increase of alpha 5 integrin on cell surface as well as the increase of alpha 5 mRNA and protein in the cells. However, the expressions of sialyl Lewis X (SLe(x), the product of alpha 1,3FucT-VII) on both alpha 5 and beta 1 integrin subunits were unchanged. Concomitantly, the tyrosine autophosphorylated FAK and dephosphorylated Src (FAK and Src involve in the signal transduction of integrin alpha 5 beta 1) were up-regulated, while the Tyr-527 phosphorylated Src was down-regulated. The above-mentioned alterations were correlated to the expressions of alpha 1,3FucT-VII in different of alpha 1,3FucT-VII transfected H7721 cell lines. In addition, after alpha 1,3FucT-VII transfection, cell adhesion to fibronectin (Fn) and chemotaxic cell migration were obviously promoted. The cell adhesion could be blocked by alpha 5 integrin antibody, and cell migration was obviously attenuated by the antibodies to both a5 integrin and SLe(x). These findings suggest that the increased surface alpha 5 integrin caused by the up-regulation of 36 mRNA promotes the cell adhesion to Fn, cell migratiom, and Fn-induced signaling of alpha 5 beta 1 integrin. The up-regulation of surface SLe(x) originated from the over expression of alpha 3FucT-VII also led to the Stimulation of cell migration. This is the first time to report that alpha 1,3FucT-VII can regulate the mRNA expression of integrin.