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

Abstract

Sirtuins, which are class III NAD-dependent histone deacetylases (HDACs) that regulate a number of physiological processes, play important roles in the regulation of metabolism, aging, oncogenesis and cancer progression. More 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 which modify steroid hormone receptors through phosphorylation. Furthermore, disruption of sirtuin activity may be an important step in the development of steroid hormone-refractory cancers.

Sirtuin1 (Sirt1) Promotes Cortical Bone Formation by Preventing β-Catenin Sequestration by FoxO Transcription Factors in Osteoblast Progenitors

“…Similar female-specific effects of Sirt1 in the skeleton have been reported by others (8). A potential explanation for these findings could be cross-talk between Sirt1 and estrogen receptor ␣ (ER␣), documented in other cell types (33). Nonetheless, in earlier work of ours, deletion of ER␣ in osteoprogenitor cells did not affect endocortical bone formation (18), suggesting that the effects of Sirt1 in osteoprogenitors are independent of ER␣.…”

Acetylation of lysine 109 modulates pregnane X receptor DNA binding and transcriptional activity

“…A likely alternative to complex recycling, which we did not test, is promoter clearance and PXR degradation. Deacetylation of FXR and LXR by SIRT1 was shown to target the receptors for ubiquitin-mediated proteasomal degradation [40, 55]. Since PXR stability is regulated by ubiquitin-mediated proteasomal degradation, this is a likely mechanism, although the role of acetylation and/or deacetylation in this context, thus far, has remained unclear [30, 31].…”

Prognostic Role of Hormone Receptors in Ovarian Cancer: A Systematic Review and Meta-Analysis

“…Disruption in the physiologic functions of hormone receptors can lead to several types of malignancies, 4 and they are currently considered to be important therapeutic targets. With the development of molecular biology and immunologic method, such as immunohistochemistry and fluorescence in situ hybridization, hormone receptors have been introduced to refine outcome prediction of female cancers, such as breast cancer, endometrium cancer, and ovarian cancer.…”