PCP4 promotes the growth and castration-resistant development of prostate cancer

Abstract Purkinje cell protein 4 (PCP4), which shows homology to the calcium-binding β-chain, regulates the calmodulin (CaM)-dependent signaling pathway by modulating CaM-dependent protein kinase 2 (CaMKK2) activity in Purkinje cells. In this work, we demonstrate that PCP4, which plays a role in tumorigenesis, induces prostate cancer (PCa) cell proliferation and migration in vitro and in vivo. Moreover, androgen receptor (AR) regulates the expression and phosphorylation activity of CaMKK2 by inducing the transcription of PCP4 in castration-resistant PCa (CRPC). Thus, exogenous overexpression of PCP4 blocks the biological function that EPI, the inhibitor of AR, suppressed the expression and phosphorylation of CaMKK2 in hormone-sensitive LNCap cells. A clinicopathological study of PCP4 was subsequently conducted on a cohort of 51 human PCa patients, and protein and mRNA expression levels of PCP4 and CaMKK2 were positively correlated with the sensitivity of androgen-deprivation treatment (p < 0.05). Moreover, PCP4 and CaMKK2 were significantly correlated with PCa relapse. This study reveals the oncogenic activity of PCP4 in vitro and provides insights into relevant mechanisms that may lead to novel treatments for CRPC.