Recently, β-arrestin1 has been indicated as a prostate cancer promoter through promoting cell proliferation and epithelial to mesenchymal transition, but its underlying mechanism remains unclear. Here, our data revealed that β-arrestin1 could promote cell growth through inhibiting the transcriptional activity and expression of FOXO3a in prostate cancer cells in vitro and in vivo. We found that β-arrestin1 could promote the cell and tumor growth of prostate cancer, and β-arrestin1 expression represented a negative correlation with FOXO3a expression but not FOXO1 expression in prostate cancer cell lines and tissues. In addition, forced expression of β-arrestin1 induced a significant decrease of FOXO3a expression but had no clear effect on FOXO1 expression. Mechanistically, β-arrestin1 could interact with FOXO3a and MDM2, respectively, and promote the interaction between FOXO3a and MDM2, whereas it had no obvious interaction with FOXO1. Furthermore, β-arrestin1 could inhibit the transcriptional activity of FOXO3a via Akt and ERK1/2 pathways. Together, our results revealed a novel mechanism for β-arrestin1 in the regulation of the prostate cancer procession through inhibiting FOXO3a.
Keywords: FOXO3a; cell growth; prostate cancer; ubiquitylation; β-arrestin1.
© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.