Expression of integrins α3β1 and α5β1 and GlcNAc β1,6 glycan branching influences metastatic melanoma cell migration on fibronectin

Eur J Cell Biol. 2013 Dec;92(12):355-62. doi: 10.1016/j.ejcb.2013.10.007. Epub 2013 Nov 1.

Abstract

Acquisition of metastatic potential is accompanied by changes in cell surface N-glycosylation. One of the best-studied changes is increased expression of N-acetylglucosaminyltransferase V enzyme (GnT-V) and its products, β1,6-branched N-linked oligosaccharides, observed in the tumorigenesis of many cancers. In this study we demonstrate that during the transition from the vertical growth phase (VGP) (WM793 cell line) to the metastatic stage (WM1205Lu line), β1,6 glycosylation of melanoma cell surface proteins increases as a consequence of elevated expression of the GnT-V-encoding Mgat-5 gene. Treatment with swainsonine led to reduced cell motility on fibronectin in both cell lines; the effect was stronger in metastatic cells, probably due to the higher content of GlcNAc β1,6-branched glycans on the main fibronectin receptors - integrins α5β1 and α3β1. Our results show that GlcNAc β1,6 N-glycosylation of cell surface receptors, which increases with the aggressiveness of melanoma cells, is an important factor influencing melanoma cell migration.

Keywords: GnT-V; Integrins; Melanoma; Migration; PHA-L; β1-6 branching.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Cell Movement
  • Fibronectins / metabolism*
  • Glycosylation
  • Humans
  • Integrin alpha3beta1 / genetics
  • Integrin alpha3beta1 / metabolism*
  • Integrin alpha5beta1 / genetics
  • Integrin alpha5beta1 / metabolism*
  • Melanoma / metabolism*
  • Melanoma / pathology
  • N-Acetylglucosaminyltransferases / metabolism
  • Neoplasm Metastasis
  • Polysaccharides / metabolism*

Substances

  • Fibronectins
  • Integrin alpha3beta1
  • Integrin alpha5beta1
  • Polysaccharides
  • N-Acetylglucosaminyltransferases
  • alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase
  • Acetylglucosamine