Upon the whole, the above results suggest that (i) Akt hyper-activation is an important event in the transition between primary and metastatic melanoma, modulating the motility and invasion capabilities of the cell (ii) the inhibitory action of IGFBP-3 on cell motility requires down-regulation of the Akt pathway, probably involving GSK3β and mTOR as downstream effectors. The gene discussed is IGFBP3; the disease is metastatic melanoma.