Loss of E-cadherin leads to upregulation of NFkappaB activity in malignant melanoma

Oncogene. 2004 Nov 4;23(52):8509-19. doi: 10.1038/sj.onc.1207831.


Malignant transformation of melanocytes frequently coincides with loss of E-cadherin expression. Here, we show that loss of E-cadherin leads to induction of nuclear factor kappa B (NFkappaB) activity in melanoma cell lines. Melanoma cells show constitutively active NFkappaB, whereas no activity is found in primary melanocytes. After re-expression of E-cadherin in melanoma cells, strong downregulation of NFkappaB activity was found. Consistently, NFkappaB activity was induced in primary human melanocytes after inhibition of E-cadherin activity by functionally blocking anti-E-cadherin antibodies. Interestingly, re-expression of E-cadherin-blocked p38 MAPK activity and the p38 MAPK inhibitors SB203580 and SB202190 almost completely prevented NFkappaB activation in melanoma cells. Furthermore, cytoplasmatic beta-catenin induced p38 and NFkappaB activation in malignant melanoma. To our knowledge, this is the first report suggesting a correlation between E-cadherin and NFkappaB activity in melanocytes and melanoma cells. In summary, we conclude that loss of E-cadherin and cytoplasmatic beta-catenin induces p38-mediated NFkappaB activation, potentially revealing an important mechanism of tumorigenesis in malignant melanomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cadherins / metabolism*
  • DNA, Antisense / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Genes, Reporter
  • Humans
  • Melanoma / metabolism*
  • NF-kappa B / metabolism*
  • Polymerase Chain Reaction
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transfection
  • Up-Regulation


  • Cadherins
  • DNA, Antisense
  • DNA-Binding Proteins
  • NF-kappa B
  • Snail Family Transcription Factors
  • Transcription Factors