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Gallagher SJ , Rambow F , Kumasaka M , Champeval D , Bellacosa A , Delmas V , Larue L
Beta-catenin inhibits melanocyte migration but induces melanoma metastasis
Oncogene. 2013 Apr 25;32(17) :2230-8
AbstractThe 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.
Notes1476-5594 Gallagher, S J Rambow, F Kumasaka, M Champeval, D Bellacosa, A Delmas, V Larue, L P30 CA006927/CA/NCI NIH HHS/United States R01 CA078412/CA/NCI NIH HHS/United States Journal Article Research Support, Non-U.S. Gov't England Oncogene. 2013 Apr 25;32(17):2230-8. doi: 10.1038/onc.2012.229. Epub 2012 Jun 4.