βKlotho inhibits androgen/androgen receptor-associated epithelial-mesenchymal transition in prostate cancer through inactivation of ERK1/2 signaling

The epithelial-mesenchymal transition (EMT) is reported to have intimate crosstalk with androgen receptor (AR) signaling in prostate cancer (PCa) and is known to be responsible for castration resistance. Fibroblast growth factor/receptor (FGF/FGFR) signaling is also involved in tumor progression and EMT in multiple tissues. Several studies have investigated the role of βKlotho, an FGF/FGFR signaling co-receptor in tumorigenesis. However, its role in PCa remains unknown. In the present study, the role of androgen in the EMT of PCa cells was examined by western blotting. The expression of βKlotho was examined in prostate cells and PCa tissues by western blotting and immunohistochemistry, respectively. The biological role of βKlotho was revealed by a series of functional in vitro and in vivo studies. We determined that βKlotho expression was significantly decreased in PCa tissues compared with benign prostatic hyperplasia (BPH) tissues, and low βKlotho expression was associated with a high Gleason score of PCa. βKlotho overexpression inhibited the viability, migration, and androgen/AR-associated EMT of PCa cells through the inactivation of ERK1/2 signaling. Notably, βKlotho overexpression inhibited prostate tumor growth and EMT in vivo. Knockdown of βKlotho produced the opposite effects. In conclusion, βKlotho inhibits EMT and plays a tumor-suppressive role in PCa, linking FGF/FGFR/βKlotho signaling to the regulation of PCa progression.