Suppression of Malignant Potentials of A549 Human Lung Cancer Cell Line by Downregulation of the β4-Galactosyltransferase 1 Gene Expression.

Our previous study demonstrated that downregulation of transcription factor Specificity protein (Sp) 1 suppresses the malignant potentials of A549 human lung cancer cell line with the reduced β4-galactosylation of highly branched N-glycans on cell surface glycoproteins. The reduced β4-galactosylation was brought about by the decreased expression of the β4-galactosyltransferase 1 (β4GalT1) gene. Herein, we examined whether the reduced β4-galactosylation by decreasing the β4GalT1 gene expression suppresses the malignant potentials of A549 cells. In the β4GalT1-downregulated cells, the β4-galactosylation of highly branched N-glycans was reduced in several glycoproteins such as lysosome-associated membrane protein-1 and E-cadherin. The anchorage-independent growth and migratory ability of the β4GalT1-downregulated cells decreased when compared with the control cells. Furthermore, the phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) decreased in the β4GalT1-downregulated cells. These results indicate that downregulation of the β4GalT1 gene decreases the β4-galactosylation of highly branched N-glycans and the phosphorylation of p44/42 MAPK, and suppresses the malignant potentials of A549 cells.