Integrin-mediated Cell Migration Is Blocked by Inhibitors of Human Neuraminidase

Biochim Biophys Acta. 2016 Sep;1861(9 Pt A):1170-1179. doi: 10.1016/j.bbalip.2016.06.013. Epub 2016 Jun 22.


Integrins are critical receptors in cell migration and adhesion. A number of mechanisms are known to regulate the function of integrins, including phosphorylation, conformational change, and cytoskeletal anchoring. We investigated whether native neuraminidase (Neu, or sialidase) enzymes which modify glycolipids could play a role in regulating integrin-mediated cell migration. Using a scratch assay, we found that exogenously added Neu3 and Neu4 activity altered rates of cell migration. We observed that Neu4 increased the rate of migration in two cell lines (HeLa, A549); while Neu3 only increased migration in HeLa cells. A bacterial neuraminidase was able to increase the rate of migration in HeLa, but not in A549 cells. Treatment of cells with complex gangliosides (GM1, GD1a, GD1b, and GT1b) resulted in decreased cell migration rates, while LacCer was able to increase rates of migration in both lines. Importantly, our results show that treatment of cells with inhibitors of native Neu enzymes had a dramatic effect on the rates of cell migration. The most potent compound tested targeted the human Neu4 isoenzyme, and was able to substantially reduce the rate of cell migration. We found that the lateral mobility of integrins was reduced by treatment of cells with Neu3, suggesting that Neu3 enzyme activity resulted in changes to integrin-co-receptor or integrin-cytoskeleton interactions. Finally, our results support the hypothesis that inhibitors of human Neu can be used to investigate mechanisms of cell migration and for the development of anti-adhesive therapies.

Keywords: Cell migration; Ganglioside; Glycolipid; Integrin; Neuraminidase; Sialidase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Cell Adhesion / drug effects
  • Cell Adhesion / genetics*
  • Cell Movement / genetics*
  • Cytoskeleton / drug effects
  • Cytoskeleton / genetics
  • Gangliosides / administration & dosage
  • HeLa Cells
  • Humans
  • Integrins / genetics*
  • Integrins / metabolism
  • Neuraminidase / antagonists & inhibitors
  • Neuraminidase / genetics*
  • Phosphorylation


  • Gangliosides
  • Integrins
  • NEU4 protein, human
  • Neu3 protein, human
  • Neuraminidase