Histone deacetylases: a saga of perturbed acetylation homeostasis in cancer.
In the current era of genomic medicine, diseases are identified as manifestations of anomalous patterns of gene expression. Cancer is the principal example among such maladies. Although remarkable progress has been achieved in the understanding of the molecular mechanisms involved in the genesis and progression of cancer, its epigenetic regulation, particularly histone deacetylation, demands further studies. Histone deacetylases (HDACs) are one of the key players in the gene expression regulation network in cancer because of their repressive role on tumor suppressor genes. Higher expression and function of deacetylases disrupt the finely tuned acetylation homeostasis in both histone and non-histone target proteins. This brings about alterations in the genes implicated in the regulation of cell proliferation, differentiation, apoptosis and other cellular processes. Moreover, the reversible nature of epigenetic modulation by HDACs makes them attractive targets for cancer remedy. This review summarizes the current knowledge of HDACs in tumorigenesis and tumor progression as well as their contribution to the hallmarks of cancer. The present report also describes briefly various assays to detect histone deacetylase activity and discusses the potential role of histone deacetylase inhibitors as emerging epigenetic drugs to cure cancer.
Department of Life Science, National Institute of Technology, Rourkela, Odisha, India (SP, SK, AS, DS, SKR, SKP).
Sabnam
S
Parbin
Swayamsiddha
S
Kar
Arunima
A
Shilpi
Dipta
D
Sengupta
Moonmoon
M
Deb
Sandip Kumar
SK
Rath
Samir Kumar
SK
Patra
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D037761:Sirtuins / Q000378:metabolism
D056572:Histone Deacetylase Inhibitors; D037761:Sirtuins; D006655:Histone Deacetylases
acetylation homeostasis; cancer; epigenetics; histone deacetylase inhibitors (HDACi); histone deacetylases (HDACs); tumor suppressor genes