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Open AccessArticle

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

1
Department of Pharmacology, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA
2
Division of Medical Oncology, University of Colorado Anschutz Medical Center. Aurora, CO 80045, USA
3
Department of Biochemistry, University of Colorado Anschutz Medical Center, Aurora, CO 80045, USA
4
Department of Cancer Biology, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157, USA
*
Author to whom correspondence should be addressed.
Cells 2019, 8(10), 1115; https://doi.org/10.3390/cells8101115
Received: 19 August 2019 / Revised: 10 September 2019 / Accepted: 18 September 2019 / Published: 20 September 2019
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. View Full-Text
Keywords: CPT1A; prostate cancer; androgen receptor; histone acetylation; enzalutamide; dihydrotestosterone CPT1A; prostate cancer; androgen receptor; histone acetylation; enzalutamide; dihydrotestosterone
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Joshi, M.; Stoykova, G.E.; Salzmann-Sullivan, M.; Dzieciatkowska, M.; Liebman, L.N.; Deep, G.; Schlaepfer, I.R. CPT1A Supports Castration-Resistant Prostate Cancer in Androgen-Deprived Conditions. Cells 2019, 8, 1115.

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