Beta-catenin inhibits melanocyte migration but induces melanoma metastasis

The canonical Wnt signalling pathway induces the beta-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/beta-catenin signalling pathway is frequently activated in melanoma, but the presence of beta-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, beta-catenin signalling decreased the migration of melanocytes and melanoma cell lines. In vivo, beta-catenin signalling in melanoblasts reduced the migration of these cells, causing a white belly-spot phenotype. The inhibition by beta-catenin of migration was dependent on MITF-M, a key transcription factor of the melanocyte lineage, and CSK, an Src-inhibitor. Despite reducing migration, beta-catenin signalling promoted lung metastasis in the NRAS-driven melanoma murine model. Thus, beta-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. Oncogene (2013) 32, 2230-2238; doi:10.1038/onc.2012.229; published online 4 June 2012