The Hexosamine Biosynthetic Pathway (HBP) is a branch of glycolysis responsible for the production of a key substrate for protein glycosylation, UDP-GlcNAc. Cancer cells present altered glucose metabolism and aberrant glycosylation, pointing to alterations on HBP. Recently it was demonstrated that HBP influences many aspects of tumor biology, including the development of metastasis. In this work we characterize HBP in melanoma cells and analyze its importance to cellular processes related to the metastatic phenotype. We demonstrate that an increase in HBP flux, as well as increased O-GlcNAcylation, leads to decreased cell motility and migration in melanoma cells. In addition, inhibition of N- and O-glycosylation glycosylation reduces cell migration. High HBP flux and inhibition of N-glycosylation decrease the activity of metalloproteases 2 and 9. Our data demonstrates that modulation of HBP and different types of glycosylation impact cell migration.
Keywords: O-GlcNAcylation; cancer; cell migration; glycosylation; hexosamine biosynthetic pathway; melanoma.