Increased substratum adhesion and beta1 integrin expression in human colon cancer cells transduced with alpha2,6 sialyltransferase (ST6Gal.I)

beta-galactoside alpha2,6 sialyltransferase (ST6Gal.I), the enzyme which adds sialic acid in alpha2,6-linkage on lactosaminic termini of glycoproteins, is frequently overexpressed in cancer. This change is associated with increased malignancy but the molecular bases of this relationship remain elusive. In this study, we have investigated the phenotypic changes related with overexpression of alpha2,6-sialylated lactosaminic chains by using clones derived from transfection of the human colon cancer cell line SW948 with the ST6Gal.I cDNA or mock transfected. Compared with untransfected cells and mock-transfectants, the ST6Gal.I-expressing clones show increased adherence to fibronectin and collagen IV but not to hyaluronic acid. Neuraminidase treatment resulted in reduced binding to fibronectin and collagen IV of a ST6Gal.I-expressing clone but in no effect on a mock-transfectant. While untransfected and mock-transfected cells tend to form multistratified tissues, ST6Gal.I-expressing clones show a flatter morphology and the tendency to grow as a monolayer. FACS analysis revealed that all ST6Gal.I-expressing clones display higher amounts of beta1 integrins on the cell surface; this difference is not supported by differences at the beta1 integrin mRNA level and is lost when cells are left in suspension for several hours, suggesting a mechanism of membrane stabilization of beta1 integrins dependent on the presence of alpha2,6-linked sialic acid. Our data support a model in which the presence of alpha2,6-linked sialic acid on membrane glycoconjugates increases the binding to extracellular matrix components, resulting in membrane stabilization of beta1 integrins, further strengthening the binding. This mechanism provides a basis for the altered phenotype associated with ST6Gal.I overexpression.