文章：

SWI/SNF核小体重塑剂与癌症

SWI/SNF nucleosome remodellers and cancer

原文发布日期：2011-06-09

DOI: 10.1038/nrc3068

类型: Review Article

开放获取: 否

要点：

1. Specific inactivating mutations in subunits of SWI/SNF chromatin remodelling complexes, including the SNF5 (also known as SMARCB1, INI1 and BAF47), ARID1A (also known as BAF250A and SMARCF1), BAF180 (also known as PBRM1) and BRM/SWI2-related gene 1 (BRG1; also known as SMARCA4) subunits, occur at a high frequency in several types of cancer.
2. Genetically engineered mice carrying mutations in Snf5 and Brg1 have established that at least some SWI/SNF subunits have bona fide tumour suppressor activity.
3. SWI/SNF complexes regulate gene expression by using the energy of ATP to remodel chromatin.
4. A central function of SWI/SNF complexes is the coordinated regulation of gene expression programmes. These complexes have essential roles during lineage specification and in the maintenance of stem cell pluripotency.
5. Emerging evidence has identified key pathways that contribute to tumorigenesis following perturbation of SWI/SNF complexes.
6. Collectively, enzymes that modify chromatin structure are emerging as key regulators of tumorigenesis. As epigenetic alterations are potentially reversible, unlike DNA mutations, the targeted inhibition of chromatin-modifying enzymes may have important therapeutic implications for cancer.

要点翻译：

1. SWI/SNF染色质重塑复合物的特定亚基失活突变在多种癌症中高频发生，这些亚基包括SNF5（亦称SMARCB1、INI1和BAF47）、ARID1A（亦称BAF250A和SMARCF1）、BAF180（亦称PBRM1）以及BRM/SWI2相关基因1（BRG1；亦称SMARCA4）。
2. 携带Snf5和Brg1基因突变的基因工程小鼠模型证实，至少部分SWI/SNF亚基具有确切的肿瘤抑制活性。
3. SWI/SNF复合物通过利用ATP能量重塑染色质来调控基因表达。
4. 该复合物的核心功能是协调基因表达程序的调控，在细胞谱系分化和维持干细胞多能性过程中发挥关键作用。
5. 最新证据揭示了SWI/SNF复合物功能紊乱后促进肿瘤发生的关键通路。
6. 总体而言，修饰染色质结构的酶类正逐渐被视为肿瘤发生的关键调控因子。表观遗传改变具有可逆性潜能（不同于DNA突变），因此靶向抑制染色质修饰酶可能为癌症治疗带来重要突破。

英文摘要：

SWI/SNF chromatin remodelling complexes use the energy of ATP hydrolysis to remodel nucleosomes and to modulate transcription. Growing evidence indicates that these complexes have a widespread role in tumour suppression, as inactivating mutations in several SWI/SNF subunits have recently been identified at a high frequency in a variety of cancers. However, the mechanisms by which mutations in these complexes drive tumorigenesis are unclear. In this Review we discuss the contributions of SWI/SNF mutations to cancer formation, examine their normal functions and discuss opportunities for novel therapeutic interventions for SWI/SNF-mutant cancers.

摘要翻译： 

SWI/SNF染色质重塑复合物利用ATP水解的能量重塑核小体并调节转录。越来越多的证据表明，这些复合物在肿瘤抑制中具有广泛作用，因为最近在多种癌症中以高频率发现了几个SWI/SNF亚基的失活突变。然而，这些复合物突变驱动肿瘤发生的机制尚不清楚。在本综述中，我们讨论了SWI/SNF突变对癌症形成的贡献，审视了它们的正常功能，并探讨了针对SWI/SNF突变癌症的新型治疗干预措施的机会。

原文链接：

SWI/SNF nucleosome remodellers and cancer