Beta-catenin inhibits melanocyte migration but induces melanoma metastasis.

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

SUBMITTER: Gallagher SJ 

PROVIDER: S-EPMC3637425 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature