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Beta-catenin inhibits melanocyte migration but induces melanoma metastasis

Oncogene volume 32, pages 2230–2238 (2013)Cite this article

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Abstract

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.

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Acknowledgements

We would like to thank D Bennett, M Herlyn and F Beermann for kindly providing materials. We thank staff from the animal colony and imaging facilities of Curie, including Y Bourgeois, F Cordelières and H Harmange in particular. SG was supported by LNCC and Curie. This work was supported by the Ligue Nationale Contre le Cancer (Equipe labellisée) and INCa.

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Author notes

  1. S J Gallagher, F Rambow and M Kumasaka: These authors contributed equally to this work.

Authors and Affiliations

  1. Centre de Recherche, Developmental Genetics of Melanocytes, Institut Curie, Orsay, France

    S J Gallagher, F Rambow, M Kumasaka, D Champeval, V Delmas & L Larue

  2. CNRS UMR3347, Orsay, France

    S J Gallagher, F Rambow, M Kumasaka, D Champeval, V Delmas & L Larue

  3. INSERM U1021, Orsay, France

    S J Gallagher, F Rambow, M Kumasaka, D Champeval, V Delmas & L Larue

  4. Fox Chase Cancer Center, Cancer Biology Program and Epigenetics and Progenitor Cells Keystone Program, Philadelphia, PA, USA

    A Bellacosa

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  1. S J Gallagher
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Correspondence to L Larue.

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Gallagher, S., Rambow, F., Kumasaka, M. et al. Beta-catenin inhibits melanocyte migration but induces melanoma metastasis. Oncogene 32, 2230–2238 (2013). https://doi.org/10.1038/onc.2012.229

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