Chromatin remodeling in cancer: a gateway to regulate gene transcription.
Chromatin remodeling in cancer: a gateway to regulate gene transcription.
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DOI：
10.1016/j.molonc.2012.09.005
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发表时间：
2012-12
影响因子：
6.6
通讯作者：
Kumar R
中科院分区：
文献类型：
--
作者：
Nair SS;Kumar R
癌细胞对不同的生存策略具有显著的适应性，这可能是由于其与正常细胞不同地解释信号线索的能力。癌细胞似乎在不断地取样、选择和调整信号通路，以促进其增殖。这种成功的适应性进化过程最终使治疗方案具有可伸缩性，从而促进癌症进展。基于大量的可用信息，现在很明显，多种信号通路最终可能以时空方式会聚到DNA模板依赖的动态过程中。考虑到真核生物基因组的复杂性和包装性，这一过程涉及到染色质重塑子介导的能量依赖性子事件。染色质重塑蛋白作为看门人的功能，并构成了辅助因子的核小体DNA的可访问性的主要决定因素，允许广泛的生物功能。因此，重塑蛋白的异常表达或表观遗传调节赋予癌细胞重新编程其基因组以维持致癌表型的独特能力。癌细胞可以独特地选择多亚基重塑蛋白质组用于致癌优势。这篇综述总结了我们目前对重塑蛋白和染色质蛋白在癌症生物学中的理解和重要性，并强调了具有或不具有双重调节功能的蛋白质的矛盾作用。我们希望对这些事件的深入了解可能为靶向癌症治疗的新策略提供下一组机会。
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.
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