Abstract
Breast cancer is a highly heterogeneous disease, encompassing many subtypes that have distinct origins, behaviors and prognoses. Although traditionally seen as a genetic disease, breast cancer is now also known to involve epigenetic abnormalities. Epigenetic regulators, such as DNA methyltransferases and histone modifying enzymes, play essential roles in gene regulation and cancer development. Dysregulation of epigenetic regulator activity has been causally linked with breast cancer pathogenesis. Hairless (HR) encodes a 130 kDa transcription factor that is essential for development and tissue homeostasis. Its role in transcription regulation is partly mediated by its interaction with multiple nuclear receptors, including thyroid hormone receptor, retinoic acid receptor-related orphan receptors, and vitamin D receptor. HR has been studied primarily in epidermal development and homeostasis. Hr-mutant mice are highly susceptible to UV- or carcinogen-induced skin tumors. Besides its putative tumor suppressor function in skin, loss of HR function has also been implicated to increase leukemia susceptibility and promote the growth of melanoma and brain cancer cells. HR has also been demonstrated to function as a histone H3 lysine 9 (H3K9) demethylase. Recent genomics studies have identified HR mutations in a variety of human cancers including breast cancer. The anticancer function and mechanism of action by HR in mammary tissue remains to be investigated. Here, we review the emerging role of HR, its histone demethylase activity and histone methylation in breast cancer development and potential for epigenetic therapy.
Targeting tumorigenicity of breast cancer stem-like cells using combination epigenetic therapy: something old and something new
