Sirtuin 1 (SIRT1) and steroid hormone receptor activity in cancer

Abstract

Sirtuins, which are class III NAD-dependent histone deacetylases that regulate a number of physiological processes, play important roles in the regulation of metabolism, aging, oncogenesis, and cancer progression. Recently, a role for the sirtuins in the regulation of steroid hormone receptor signaling is emerging. In this mini-review, we will summarize current research into the regulation of estrogen, androgen, progesterone, mineralocorticoid, and glucocorticoid signaling by sirtuins in cancer. Sirtuins can regulate steroid hormone signaling through a variety of molecular mechanisms, including acting as co-regulatory transcription factors, deacetylating histones in the promoters of genes with nuclear receptor-binding sites, directly deacetylating steroid hormone nuclear receptors, and regulating pathways that modify steroid hormone receptors through phosphorylation. Furthermore, disruption of sirtuin activity may be an important step in the development of steroid hormone-refractory cancers.