Unlike low grade malignant cells, where ETS-1 represses miR-222 transcription, in metastatic melanomas ETS-1 and miR-222 appear directly interconnected by a deregulated feedback loop whereby the persistent activation of the MAPK-ERK1/2 cascade leads to Thr-38 phosphorylation of ETS-1 and miR-222 induction, in turn increasing proliferation and tumor malignancy (Felicetti et al., 2008). Here, ETS1 is linked to metastatic melanoma.