Ras oncogene directs expression of a differentially sialylated, functionally altered ß1 integrin.

Intense investigation has centered on understanding the regulation of integrin cell adhesion receptors. In the present study, we propose that variant N-glycosylation represents an important mechanism for regulation of ß1, but not ß3 or ß5 integrins. We find that expression of oncogenic ras in HD3 colonocytes causes increased a2-6 sialylation of ß1 integrins, whereas expression of dominant-negative ras induces decreased a2-6 sialylation, relative to cells with wild-type ras. In contrast, neither ß3 nor ß5 integrins are a2-6 sialylated, regardless of the state of ras activation. Results from RT-PCR analyses suggest that differential integrin sialylation is due to a ras-dependent alteration in the expression of ST6Gal I, the enzyme that adds a2-6-linked sialic acids. Cells that express differentially sialylated ß1 integrins exhibit altered adhesion to collagen I (a ß1 ligand), but not to vitronectin (a ß3 or ß5 ligand). Similarly, the enzymatic removal of cell surface sialic acids from control cells alters binding to collagen, but not to vitronectin. Finally, using a cell-free receptor/ligand-binding assay, we show that purified, desialylated a1ß1 integrins have diminished collagen-binding capability, providing strong evidence that sialic acids play a causal role in regulating ß1 integrin function.Oncogene (2003) 22, 7137-7145. doi:10.1038/sj.onc.1206834 [ABSTRACT FROM AUTHOR]