Recently, beta-arrestin1 was indicated as a tumor promoter in prostate cancer, but its exact role in cancer metastasis still have not been well clarified. Here, our data revealed that beta-arrestin1 could promote the migration and invasion of prostate cancer cells via initiating epithelial-mesenchymal transition (EMT). Mechanically, beta-arrestin1 could increase the transcriptional activity and expression of beta-catenin, together with Akt activity, whereas decrease the activities of GSK-3 beta and PP2A. In addition, beta-arrestin1 could function as a scaffold protein in modulating the interactions between PP2A, Akt, GSK-3 beta and beta-catenin. These results reveal a novel mechanism of beta-arrestin1 in modulating EMT and GSK-3 beta/beta-catenin signaling in prostate cancer, thereby suggest that assessment of beta-arrestin1 may provide a potential therapeutic target for prostate cancer. (C) 2016 Elsevier Inc. All rights reserved.