Targeting Invasive Properties of Melanoma Cells

Imanol Arozarena, Claudia Wellbrock

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Melanoma is a skin cancer notorious for its metastatic potential. As an initial
step of the metastatic cascade melanoma cells part from the primary tumour and invade the surrounding tissue, which is crucial for their dissemination and the formation of distant secondary tumours. Over the last two decades our understanding of both, general and melanoma specific mechanisms of invasion has significantly improved, but to date no efficient therapeutic strategy tackling the invasive properties of melanoma cells has reached the clinic. In this review we assess the major contributions towards understanding of the molecular biology of melanoma cell invasion with a focus on melanoma specific traits. These traits are based on the neural crest origin of melanoma cells and explain their intrinsic invasive nature. A particular emphasis is given to lineage specific signalling mediated by TGFβ, and non-canonical and canonical WNT signalling, but also to the role of PDE5A and Rho-GTPases in modulating modes of melanoma cell invasion. We discuss existing caveats in the current understanding of the metastatic properties of melanoma cells, as well as the relevance of the ‘phenotype switch’ model and ‘co-operativity’ between different phenotypes in heterogeneous tumours. At the centre of these phenotypes is the lineage commitment factor MITF, one of the most crucial regulators of the balance between de-differentiation (neural-crest specific gene expression) and differentiation (melanocyte specific gene expression) that defines invasive and non-invasive melanoma cell phenotypes. Finally, we provide insight into the current evidence linking resistance to targeted therapies to invasive properties of melanoma cells.
Original languageEnglish
JournalFEBS Journal
Issue number14
Early online date14 Feb 2017
Publication statusPublished - 2017

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


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