Department of Urology, Minimally Invasive Surgery Center, the First Affiliated Hospital of Guangzhou Medical University, Guangdong Key Laboratory of Urology, Guangzhou Institute of Urology, Guangzhou, China.
Department of Oncology, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Cancer Sci. 2018 Jun;109(6):1834-1842. doi: 10.1111/cas.13619. Epub 2018 May 26.
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.
最近，β-arrestin1 被认为是通过促进细胞增殖和上皮间质转化来促进前列腺癌的发生的，但它的潜在机制尚不清楚。在这里，我们的数据显示，β-arrestin1 可以通过抑制 FOXO3a 在前列腺癌细胞中的转录活性和表达来促进细胞生长，无论是在体外还是体内。我们发现，β-arrestin1 可以促进前列腺癌细胞和肿瘤的生长，β-arrestin1 的表达与 FOXO3a 的表达呈负相关，但与 FOXO1 的表达无关，在前列腺癌细胞系和组织中。此外，强制表达β-arrestin1 会导致 FOXO3a 的表达明显下降，但对 FOXO1 的表达没有明显影响。在机制上，β-arrestin1 可以分别与 FOXO3a 和 MDM2 相互作用，并促进 FOXO3a 和 MDM2 之间的相互作用，而与 FOXO1 没有明显的相互作用。此外，β-arrestin1 可以通过 Akt 和 ERK1/2 通路抑制 FOXO3a 的转录活性。综上所述，我们的研究结果揭示了β-arrestin1 通过抑制 FOXO3a 来调节前列腺癌发生发展的新机制。
