Lung cancer metastasis-related protein 1 promotes the transferring from advanced metastatic prostate cancer to castration-resistant prostate cancer by activating the glucocorticoid receptor α signal pathway

Abstract

ABSTRACT Androgen deprivation therapy is currently the main therapeutic strategy for the treatment of advanced metastatic prostate cancer (ADPC). However, the tumor type in ADPC patients transforms into castration-resistant prostate cancer (CRPC) after 18–24 months of treatments, the underlying mechanism of which remains unclear. The present study aimed to investigate the potential pathological mechanism of the conversion from ADPC to CRPC by exploring the function of lung cancer metastasis-related protein 1 (LCMR1). We found that LCMR1 and glucocorticoid receptor α (GRα) were highly expressed in CRPC tissues, compared to ADPC tissues, and were accompanied by high concentrations of inflammatory factors. Knocking down LCMR1 or GRα in CRPC cells led to inhibition of metastasis and proliferation and induction of apoptosis. The expression of HSP90 and IL-6 was upregulated and that of androgen receptor was downregulated by knocking down LCMR1 or GRα in CRPC cells. Luciferase assay results indicated that the transcription of GRα was promoted by the LCMR1 promoter. The growth rate of CRPC cells in vivo was greatly decreased by knocking down LCMR1 or GRα. Lastly, CRPC cell sensitivity to enzalutamide treatment was found significantly enhanced by the knockdown of LCMR1. Taken together, LCMR1 might regulate the conversion of ADPC to CRPC by activating the GRα signaling pathway.