alpha1,3 fucosyltransferase-VII up-regulates the mRNA of alpha5 integrin and its biological function.
After transfection of alpha1,3fucosyltransferase (FucT)-VII cDNA into H7721 human hepatocarcinoma cells, the expression of alpha5, but not beta1 integrin was significantly up-regulated. This was evidenced by the increase of alpha5 integrin on cell surface as well as the increase of alpha5 mRNA and protein in the cells. However, the expressions of sialyl Lewis X (SLe(x), the product of alpha1,3FucT-VII) on both alpha5 and beta1 integrin subunits were unchanged. Concomitantly, the tyrosine autophosphorylated FAK and dephosphorylated Src (FAK and Src involve in the signal transduction of integrin alpha5beta1) were up-regulated, while the Tyr-527 phosphorylated Src was down-regulated. The above-mentioned alterations were correlated to the expressions of alpha1,3FucT-VII in different alpha1,3FucT-VII transfected H7721 cell lines. In addition, after alpha1,3FucT-VII transfection, cell adhesion to fibronectin (Fn) and chemotaxic cell migration were obviously promoted. The cell adhesion could be blocked by alpha5 integrin antibody, and cell migration was obviously attenuated by the antibodies to both alpha5 integrin and SLe(x). These findings suggest that the increased surface alpha5 integrin caused by the up-regulation of alpha5 mRNA promotes the cell adhesion to Fn, cell migratiom, and Fn-induced signaling of alpha5beta1 integrin. The up-regulation of surface SLe(x) originated from the over expression of alpha1,3FucT-VII also led to the stimulation of cell migration. This is the first time to report that alpha1,3FucT-VII can regulate the mRNA expression of integrin.
Wang
Qiu-Yan
QY
Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry, Shanghai Medical college, Fudan University, Shanghai 200032, China.
Zhang
Ying
Y
Shen
Zong-Hou
ZH
Chen
Hui-Li
HL
D000906:Antibodies / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D005647:Fucosyltransferases / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics* / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D014162:Transfection; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
D000906:Antibodies; D018076:DNA, Complementary; D039482:Integrin alpha5; D019012:Integrin beta1; D009844:Oligosaccharides; D021122:Protein Subunits; D012333:RNA, Messenger; D000080506:Sialyl Lewis X Antigen; C502597:FUT7 protein, human; D005647:Fucosyltransferases; D051417:Focal Adhesion Kinase 1; D016392:Proto-Oncogene Proteins pp60(c-src)