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Therefore, it is possible that there are at least two distinct mechanisms for circulating melanoma cells to successfully establish at the secondary site depending on if they are active or dormant cancer cells: 1) the canonical extravasation or 2) the proposed transition of a quiescent-like endothelial melanoma cell to convert into a mesenchymal phenotype in order to successfully extravasate into the metastatic niche ( Figure 3 ) (73, 78)

MOTS-c activates AMPK (AMP-activated protein kinase), the master metabolic switch that signals cells to burn fat when energy is low

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