Membrane sialidase NEU3 is highly expressed in human melanoma cells promoting cell growth with minimal changes in the composition of gangliosides

Cancer Sci. 2011 Dec;102(12):2139-49. doi: 10.1111/j.1349-7006.2011.02086.x. Epub 2011 Oct 17.

Abstract

NEU3 is a membrane sialidase specific for gangliosides. Its increased expression and implication in some cancers have been reported. Here, we analyzed NEU3 expression in malignant melanoma cell lines and its roles in the cancer phenotypes. Quantitative RT-PCR revealed that high levels of the NEU3 gene were expressed at almost equivalent levels with those in colon cancers. To examine the effects of overexpression of NEU3, NEU3 cDNA-transfectant cells were established using a melanoma cell line SK-MEL-28 and its mutant N1 lacking GD3. SK-MEL-28 sublines overexpressing both the NEU3 gene and NEU3 enzyme activity showed no changes in both cell growth and ganglioside expression, while N1 cells showed a mild increase in cell proliferation with increased phosphorylation of the EGF receptor and neo-synthesis of Gb3 after NEU3 transfection. In contrast, NEU3 silencing resulted in a definite reduction in cell growth in a melanoma line MeWo, while ganglioside patterns underwent minimal changes. Phosphorylation levels of ERK1/2 with serum stimulation decreased in the NEU3-silenced cells. All these results suggest that NEU3 is highly expressed to enhance malignant phenotypes including apoptosis inhibition in malignant melanomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Tumor-Associated, Carbohydrate / biosynthesis
  • Apoptosis
  • Cell Line, Tumor
  • Cell Proliferation*
  • Colonic Neoplasms / metabolism
  • ErbB Receptors / metabolism
  • Gangliosides / metabolism*
  • Humans
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neuraminidase / biosynthesis*
  • Neuraminidase / genetics
  • RNA Interference
  • RNA, Small Interfering

Substances

  • Antigens, Tumor-Associated, Carbohydrate
  • Gangliosides
  • Gb3 antigen
  • Neoplasm Proteins
  • RNA, Small Interfering
  • ErbB Receptors
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Neu3 protein, human
  • Neuraminidase