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.
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We are in debt to our colleagues in this field whose original work may have not been cited here due to space limitations. The chromatin remodeling and signaling work in Kumar laboratory is being supported by grants from the National Institutes of Health grants CA98823 and CA090970. The Li laboratory is funded by the National Natural Science Foundation of China (Number 81372847 and 81572584), the Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning (Number 2013-06) and the Innovation Program of Shanghai Municipal Education Commission (Number 2015ZZ007). The Knapp laboratory is supported by the Structural Genomic Consortium, a registered charity (number 1097737) that receives funds from AbbVie, Bayer Pharma AG, Boehringer Ingelheim, the Canada Foundation for Innovation, the Eshelman Institute for Innovation, the Genome Canada, the Innovative Medicines Initiative (EU/EFPIA), Janssen, Merck & Co., Novartis Pharma AG, the Ontario Ministry of Economic Development and Innovation, Pfizer, the São Paulo Research Foundation-FAPESP, Takeda, and the Welcome Trust.
The authors declare no conflict of interest.
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Kumar, R., Li, DQ., Müller, S. et al. Epigenomic regulation of oncogenesis by chromatin remodeling. Oncogene 35, 4423–4436 (2016). https://doi.org/10.1038/onc.2015.513
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