Impaired Akt activity gauged by the marked decrease in p-FoxO3a(S253) expression may contribute to the retention of FoxO3a in the nucleus of Smurf2 knockdown cells, thereby promoting its tumor suppressor functions, by upregulating the expression of FoxO-responsive genes such as p27/Kip1 and p21/waf1. This evidence concerns the gene CDKN1A and neoplasm.