β1,6-branched complex-type N-glycans affect FAK signaling in metastatic melanoma cells

ABSTRACT

Integrin-dependent binding of the cell to extracellular matrix (ECM) is a key activator of the focal adhesion kinase (FAK) signaling pathway. N-glycosylation of integrins affects their interactions with ECM proteins. Using WM266-4 cells with overexpression of β1,6-acetylglucosaminyltransferase V, we showed that β1,6-branched N-glycans increased tyrosine phosphorylation of FAK in metastatic melanoma cells, resulting in enhanced migration on vitronectin (VN). The co-localization of α_vβ₃ integrin and FAK in focal adhesions of melanoma cells growing on VN indicates their interaction in signal transduction. Melanoma cell migration on VN was mediated by α_vβ₃ caring overexpressed β1,6-branched structures, important for FAK upregulation.

Keywords:

• β1
• 6-branched N-glycans
• α_vβ₃ integrin
• Focal adhesion kinase
• Melanoma
• Vitronectin