Chromatin remodeling in Cancer: A Gateway to regulate gene Transcription

Cancer cells are remarkably adaptive to diverse survival strategies, probably due to its ability to interpret signaling cues differently than the normal cells. It appears as if cancer cells are constantly sampling, selecting and adapting signaling pathways to favor its proliferation. This process of successful adaptive evolution eventually renders a retractile nature to therapeutic regimens, fueling to the process of cancer progression. Based on plethora of available information, it is now evident that multiple signaling pathways eventually converge, perhaps, in a tempo-spatial manner, onto DNA template-dependent dynamic processes. Considering the complexity and packaging of eukaryotic genome, this process involves energy-dependent sub-events mediated by chromatin remodelers. Chromatin remodeler proteins function as gatekeepers and constitute a major determinant of accessibility of accessory factors to nucleosome DNA, allowing a wide repertoire of biological functions. And thus, aberrant expression or epigenetic modulation of remodeler proteins confers a unique ability to cancer cells to reprogram its genome for the maintenance of oncogenic phenotypes. Cancer cells can uniquely select a multi-subunit remodeler proteome for oncogenic advantage. This review summarizes our current understanding and importance of remodeler and chromatin proteins in cancer biology and also highlights the paradoxical role of proteins with or without dual-regulator functions. It is our hope that an in-depth understanding of these events is likely to provide a next set of opportunities for novel strategies for targeted cancer therapeutics. (c) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.