ABSTRACT Small activating RNAs are a recently discovered group of small, noncoding, and double-stranded RNA molecules that can induce sequence-specific transcriptional gene activation by targeting gene promoter regions. In the present study, we demonstrate that induction of E-cadherin expression by small activating RNA leads to suppression of migration and invasion of PC3 prostate cancer cells. The inhibitory effect was associated with relocalization of β -catenin from the nucleus to the plasma membrane and decreased β -catenin-mediated transactivation. These data suggest that activation of E-cadherin by small activating RNA may have a therapeutic benefit for prostate and other types of cancer.