Using a metastatic melanoma model (in which B16F10 cells were injected i.v. with a melanoma cell line that could kill NK cells and metastasize to the lungs), we showed that selective deletion of Smad4 from murine NK cells dramatically reduced the rejection of tumor cells, augmenting tumor cell metastasis and impeding NK cell maturation and homeostasis (19). This evidence concerns the gene SMAD4 and melanoma.