Influence of the cytoplasmic domain of E-cadherin on endogenous N-cadherin expression in malignant melanoma

Oncogene. 2006 Jan 12;25(2):248-59. doi: 10.1038/sj.onc.1209054.


E-cadherin is known to be an important molecule in epithelial-mesenchymal transition (EMT). Malignant transformation of melanocytes frequently attends with loss of E-cadherin expression and induction of expression of mesenchymal molecules like N-cadherin. The switch of the cadherin class is an interesting phenomenon of melanoma cells and in EMT in general. Therefore, we analysed the capacity of E-cadherin to regulate expression of N-cadherin in melanocytic cells. Our experiments revealed that melanoma cells downregulate endogenous N-cadherin expression after transient transfection of full-length E-cadherin, but also of the cytoplasmic domain of E-cadherin. Therefore, we concluded that the extracellular domain of E-cadherin and cell-cell contacts are not necessary for negative regulation of N-cadherin. Melanoma cells re-expressing full-length or cytoplasmatic E-cadherin have reduced NFkappaB activity in comparison to mock-transfected cells. Downregulation of NFkappaB activity, either directly or by re-expression of E-cadherin, led to a suppression of N-cadherin promoter activity and N-cadherin expression. Consequently, an NFkappaB-binding site in the N-cadherin promoter was characterized. In summary, our results suggest that N-cadherin is directly regulated by E-cadherin. Loss of E-cadherin induces NFkappaB activity and N-cadherin expression in tumorigenic EMT.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Blotting, Western
  • Cadherins / genetics*
  • Cadherins / metabolism*
  • Cadherins / pharmacology*
  • Cell Movement
  • Cytoplasm / metabolism*
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Melanocytes / cytology
  • Melanocytes / metabolism
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasm Invasiveness / pathology
  • Promoter Regions, Genetic / genetics
  • Protein Structure, Tertiary
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology
  • Transcription, Genetic
  • Transfection


  • Cadherins
  • NF-kappa B