Beta-catenin inhibits melanocyte migration but induces melanoma metastasis.

ABSTRACT

The canonical Wnt signalling pathway induces the ß-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/ß-catenin signalling pathway is frequently activated in melanoma, but the presence of ß-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, ß-catenin signalling decreased the migration of melanocytes and melanoma cell lines. In vivo, ß-catenin signalling in melanoblasts reduced the migration of these cells, causing a white belly-spot phenotype. The inhibition by ß-catenin of migration was dependent on MITF-M, a key transcription factor of the melanocyte lineage, and CSK, an Src-inhibitor. Despite reducing migration, ß-catenin signalling promoted lung metastasis in the NRAS-driven melanoma murine model. Thus, ß-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.