SMAD6 and breast cancer: However, Smad6 can prevent the phosphorylation of other Smad members and therefore act as a negative regulator of the TGFβ mediated pathway (Imamura et al. 1997) and previous studies have shown that silencing CCN5/WISP2 expression in the breast cancer cell line MCF-7 decreases Smad6 expression levels (Sabbah et al. 2011).