Functional genomic studies reveal the androgen receptor as a master regulator of cellular energy metabolism in prostate cancer

Abstract

Sex-steroid hormones have been investigated for decades for their oncogenic properties in hormone-dependent cancers. The increasing body of knowledge on the biological actions of androgens in prostate cancer has led to the development of several targeted therapies that still represent the standard of care for cancer patients to this day. In the prostate, androgens promote cellular differentiation and proper tissue development. These hormones also promote the aberrant proliferation and survival of prostate cancer cells. Over the past few years, sequencing technologies for functional genomic analyses have rapidly expanded, revealing novel functions of sex-steroid hormone receptors other than their classic roles. In this article, we will focus on transcriptomic- and genomic-based evidence that demonstrates the importance of the androgen receptor signaling in the regulation of prostate cancer cell metabolism. This is significant because the reprogramming of cell metabolism is a hallmark of cancer. In fact, it is clear now that the androgen receptor contributes to the reprogramming of specific cellular metabolic pathways that promote tumor growth and disease progression, including aerobic glycolysis, mitochondrial respiration, fatty acid ß-oxidation, and de novo lipid synthesis. Overall, beyond regulating development, differentiation, and proliferation, the androgen receptor is also a master regulator of cellular energy metabolism.