TGF-β1, another member of the TGF-β superfamily enhances EMT and bone metastasis in breast cancer cells, including MDA-MB-231 cells, via Smad4 dependent mechanisms35, although it plays dual roles in carcinogenesis in breast cancer, being both a tumor suppressor and a tumor promoter depending on the tumor stage54. This evidence concerns the gene SMAD4 and breast carcinoma.