CPT1A Supports Castration-Resistant Prostate Cancer in Androgen-Deprived Conditions.

Joshi Joshi,Salzmann-Sullivan Salzmann-Sullivan,Stoykova Stoykova,Schlaepfer Schlaepfer,Deep Deep,Dzieciatkowska Dzieciatkowska,Liebman Liebman

doi:10.3390/cells8101115

Abstract

Prostate cancer (PCa) is the most common cancer in men, and the global burden of the disease is rising. The majority of PCa deaths are due to metastasis that are highly resistant to current hormonal treatments; this state is called castration-resistant prostate cancer (CRPC). In this study, we focused on the role of the lipid catabolism enzyme CPT1A in supporting CRPC growth in an androgen-dependent manner. We found that androgen withdrawal promoted the growth of CPT1A over-expressing (OE) tumors while it decreased the growth of CPT1A under-expressing (KD) tumors, increasing their sensitivity to enzalutamide. Mechanistically, we found that CPT1A-OE cells burned more lipid and showed increased histone acetylation changes that were partially reversed with a p300 specific inhibitor. Conversely, CPT1A-KD cells showed less histone acetylation when grown in androgen-deprived conditions. Our results suggest that CPT1A supports CRPC by supplying acetyl groups for histone acetylation, promoting growth and antiandrogen resistance.

Highlights

Prostate cancer (PCa) is the most common cancer in men [1], and the global burden of the disease is rising
The KD cells were generated with the same shRNA that was recently used in LNCaP cells in a previous publication [18]
We focused on the role of growth in an androgen-dependent this report, we focused on the role of CPT1A in supporting castration-resistant prostate cancer (CRPC) growth in an androgen-dependent manner

Summary

Introduction

Prostate cancer (PCa) is the most common cancer in men [1], and the global burden of the disease is rising. The majority of PCa deaths are due to metastasis that are highly resistant to current hormonal treatments [2,3]. Androgen-deprivation treatment (ADT) is currently the standard treatment for PCa that is localized or metastatic. Despite initial benefits of the androgen removal, some patient’s progress to an advanced disease state called castration-resistant prostate cancer (CRPC). This is the lethal form of the disease with limited treatment options, and it is still dependent on the androgen and androgen receptor (AR) axis. The main problem with using these potent AR inhibitors is the emergence of

Methods

Results

Conclusion