The Roles of Histone Deacetylases in the Regulation of Ovarian Cancer Metastasis

Abstract

Ovarian cancer is the most lethal gynecologic malignancy, and metastasis is the major cause of death in patients with ovarian cancer, which is regulated by the coordinated interplay of genetic and epigenetic mechanisms. Histone deacetylases (HDACs) are enzymes that can catalyze the deacetylation of histone and some non-histone proteins and that are involved in the regulation of a variety of biological processes via the regulation of gene transcription and the functions of non-histone proteins such as transcription factors and enzymes. Aberrant expressions of HDACs are common in ovarian cancer. Many studies have found that HDACs are involved in regulating a variety of events associated with ovarian cancer metastasis, including cell migration, invasion, and the epithelial–mesenchymal transformation. Herein, we provide a brief overview of ovarian cancer metastasis and the dysregulated expression of HDACs in ovarian cancer. In addition, we discuss the roles of HDACs in the regulation of ovarian cancer metastasis. Finally, we discuss the development of compounds that target HDACs and highlight their importance in the future of ovarian cancer therapy.

Clinical Significance of the Immunohistochemical Expression of Histone Deacetylases (HDACs)-2, -4 and -5 in Ovarian Adenocarcinomas

“…In the last decade, a variety of compounds that can block the deacetylase activity of HDACs have been recognized, and synthetic or natural molecules targeting class I, II, and IV HDACs have been developed [29]. Moreover, preclinical studies have found that HDAC inhibitors (HDACis) are able to inhibit ovarian cancer cell growth in vitro and in vivo by inhibiting the cell cycle and inducing mitotic defects through histone-mediated and histone-independent interactions [30].…”

“…Moreover, preclinical studies have found that HDAC inhibitors (HDACis) are able to inhibit ovarian cancer cell growth in vitro and in vivo by inhibiting the cell cycle and inducing mitotic defects through histone-mediated and histone-independent interactions [30]. Recently, numerous clinical trials investigate the role of HDACis alone or in combination with other drugs in patients with epithelial ovarian cancer, showing encouraging anti-tumor effects [29], especially when combined with other chemotherapeutics. This combination seems to show chemosensitizing or synergistic antitumor efficacy, which may be due to their ability to overcome particular mechanisms associated with drug resistance [31].…”