Beta-catenin inhibits melanocyte migration but induces melanoma metastasis

Oncogene. 2013 Apr 25;32(17):2230-8. doi: 10.1038/onc.2012.229. Epub 2012 Jun 4.


The canonical Wnt signalling pathway induces the β-catenin/lymphoid enhancer factor transcription factors. It is activated in various cancers, most characteristically carcinomas, in which it promotes metastatic spread by increasing migration and/or invasion. The Wnt/β-catenin signalling pathway is frequently activated in melanoma, but the presence of β-catenin in the nucleus does not seem to be a sign of aggressiveness in these tumours. We found that, unlike its positive role in stimulating migration and invasion of carcinoma cells, β-catenin signalling decreased the migration of melanocytes and melanoma cell lines. In vivo, β-catenin signalling in melanoblasts reduced the migration of these cells, causing a white belly-spot phenotype. The inhibition by β-catenin of migration was dependent on MITF-M, a key transcription factor of the melanocyte lineage, and CSK, an Src-inhibitor. Despite reducing migration, β-catenin signalling promoted lung metastasis in the NRAS-driven melanoma murine model. Thus, β-catenin may have conflicting roles in the metastatic spread of melanoma, repressing migration while promoting metastasis. These results highlight that metastasis formation requires a series of successful cellular processes, any one of which may not be optimally efficient.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CSK Tyrosine-Protein Kinase
  • Cell Line, Tumor
  • Cell Movement*
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / secondary
  • Melanocytes / physiology*
  • Melanoma / metabolism*
  • Melanoma / secondary
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Nude
  • Mice, Transgenic
  • Microphthalmia-Associated Transcription Factor / metabolism
  • Neoplasm Transplantation
  • Wnt Signaling Pathway
  • beta Catenin / physiology*
  • src-Family Kinases / metabolism


  • MITF protein, human
  • Membrane Proteins
  • Microphthalmia-Associated Transcription Factor
  • beta Catenin
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • GTP Phosphohydrolases
  • NRAS protein, human