title: Epigenomic regulation of oncogenesis by chromatin remodeling.
abstract: Disruption of the intricate gene expression program represents one of major driving factors for the development, progression and maintenance of human cancer, and is often associated with acquired therapeutic resistance. At the molecular level, cancerous phenotypes are the outcome of cellular functions of critical genes, regulatory interactions of histones and chromatin remodeling complexes in response to dynamic and persistent upstream signals. A large body of genetic and biochemical evidence suggests that the chromatin remodelers integrate the extracellular and cytoplasmic signals to control gene activity. Consequently, widespread dysregulation of chromatin remodelers and the resulting inappropriate expression of regulatory genes, together, lead to oncogenesis. We summarize the recent developments and current state of the dysregulation of the chromatin remodeling components as the driving mechanism underlying the growth and progression of human tumors. Because chromatin remodelers, modifying enzymes and protein-protein interactions participate in interpreting the epigenetic code, selective chromatin remodelers and bromodomains have emerged as new frontiers for pharmacological intervention to develop future anti-cancer strategies to be used either as single-agent or in combination therapies with chemotherapeutics or radiotherapy.
authors.affiliation: Department of Biochemistry and Molecular Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, USA.|Cancer Biology Program, Rajiv Gandhi Center of Biotechnology, Thiruvananthapuram, India.
authors.forename: R
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Shanghai Cancer Center and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.|Key Laboratory of Breast Cancer in Shanghai, Shanghai Medical College, Fudan University, Shanghai, China.|Key Laboratory of Epigenetics in Shanghai, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: D-Q
authors.initials: DQ
authors.lastname: Li
authors.affiliation: Nuffield Department of Clinical Medicine, Old Road Campus, Oxford University, Oxford, UK.|Department of Pharmaceutical Chemistry and Buchmann Institute for Life Sciences, Riedberg Campus, Frankfurt am Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Müller
authors.affiliation: Nuffield Department of Clinical Medicine, Old Road Campus, Oxford University, Oxford, UK.|Department of Pharmaceutical Chemistry and Buchmann Institute for Life Sciences, Riedberg Campus, Frankfurt am Main, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Knapp
mesh_terms: D000251:Adenosine Triphosphatases / Q000502:physiology; D000818:Animals; D063646:Carcinogenesis; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology; D004265:DNA Helicases / Q000502:physiology; D057890:Epigenomics; D006801:Humans; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex / Q000502:physiology; D009369:Neoplasms / Q000235:genetics / Q000628:therapy; D009687:Nuclear Proteins / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C086468:ISWI protein; D009687:Nuclear Proteins; D014157:Transcription Factors; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D000251:Adenosine Triphosphatases; C084108:SMARCA4 protein, human; C409462:SMARCA5 protein, human; D004265:DNA Helicases