Emerging Themes in Mechanisms of Tumorigenesis by SWI/SNF Subunit Mutation.
Emerging Themes in Mechanisms of Tumorigenesis by SWI/SNF Subunit Mutation.
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DOI：
10.1177/25168657221115656
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发表时间：
2022
影响因子：
2.2
通讯作者：
Weissmiller, April M.
中科院分区：
文献类型：
--
作者：
Jones, Cheyenne A.;Tansey, William P.;Weissmiller, April M.
关键词：
SWI/SNF染色质重塑复合物使用ATP水解的能量来改变DNA和核小体之间的接触，使基因组区域变得可用于生物过程，如转录。SWI/SNF染色质重塑也是癌症中最常见的改变蛋白质复合物之一，超过20%的所有癌症在SWI/SNF亚基中携带突变。在过去的十年中，密集的研究已经探索了与癌症中SWI/SNF功能障碍相关的分子事件，并且开始出现肿瘤相关SWI/SNF突变如何促进恶性肿瘤的共同主题。在这篇综述中，我们总结了目前对SWI/SNF复合物的理解，它们在癌症中的改变，以及这些突变对肿瘤相关转录事件的影响。我们讨论了增强子失调是如何在SWI/SNF突变型癌症的一个共同的主题，并描述了增强子和超级增强子活性的改变如何共同阻止发育和分化，同时促进干细胞和自我更新。我们还确定了第二个新兴的主题，其中SWI/SNF扰动与有效的癌蛋白转录因子AP-1和MYC交叉，以驱动恶性转录程序。
The SWI/SNF chromatin remodeling complex uses the energy of ATP hydrolysis to alter contacts between DNA and nucleosomes, allowing regions of the genome to become accessible for biological processes such as transcription. The SWI/SNF chromatin remodeler is also one of the most frequently altered protein complexes in cancer, with upwards of 20% of all cancers carrying mutations in a SWI/SNF subunit. Intense studies over the last decade have probed the molecular events associated with SWI/SNF dysfunction in cancer and common themes are beginning to emerge in how tumor-associated SWI/SNF mutations promote malignancy. In this review, we summarize current understanding of SWI/SNF complexes, their alterations in cancer, and what is known about the impact of these mutations on tumor-relevant transcriptional events. We discuss how enhancer dysregulation is a common theme in SWI/SNF mutant cancers and describe how resultant alterations in enhancer and super-enhancer activity conspire to block development and differentiation while promoting stemness and self-renewal. We also identify a second emerging theme in which SWI/SNF perturbations intersect with potent oncoprotein transcription factors AP-1 and MYC to drive malignant transcriptional programs.
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