p21 mediates activin-induced growth suppression and counteracts activin-induced SMAD4-independent migration in the presence of SMAD4.

<p>A) FET cells were treated with either scramble (SC) or p21 specific siRNA (KD). Growth suppression was assessed by MTT-metabolic assay following activin treatment. Activin induced cell growth inhibition in the presence of p21, but the effect was reversed in the absence of p21 (*p<0.05). B) Total viability is decreased in SMAD4 wild type colon cancers following activin treatment in the presence of p21. FET cells were treated with either scramble or p21 specific siRNA. Cell viability was assessed by trypan blue staining following activin treatment. Trypan blue positive cells after activin treatment were decreased in presence of p21, but increased after p21 knockdown (***p<0.001). C) Activin (A) induces cell migration in SMAD4-positive and SMAD4-negative cell lines. Cellular migration is induced in <i>SMAD</i>4-wild type FET cells and <i>SMAD4</i>-null SW480 cells following activin treatment, but more pronounced induction of migration is seen in the absence of SMAD4. Loss of p21 leads to an increase in baseline migration in SMAD4 expressing cells (*p<0.05, **p<0.01, ***p<0.001). D) p21 knockdown increases the overall pro-migratory effect of activin in FET cells. Loss of p21 in the absence of SMAD4 does further increase migratory induction (*p<0.05, ** p<0.01).