Reduced SIRT1 levels in HMLER breast cancer cells led to increased metastases in nude mice, and SIRT1 reduces the EMT in cancer and fibrosis by deacetylating Smad4 and repressing the effect of transforming growth factor-β signalling on matrix metalloproteinase-7 (MMP-7), a Smad4 target gene [30]. This evidence concerns the gene SMAD4 and cancer.