文章：

黏结癌生物学的新兴主题

Emerging themes in cohesin cancer biology

原文发布日期：2020-06-08

DOI: 10.1038/s41568-020-0270-1

类型: Review Article

开放获取: 否

英文摘要：

Mutations of the cohesin complex in human cancer were first discovered ~10 years ago. Since then, researchers worldwide have demonstrated that cohesin is among the most commonly mutated protein complexes in cancer. Inactivating mutations in genes encoding cohesin subunits are common in bladder cancers, paediatric sarcomas, leukaemias, brain tumours and other cancer types. Also in those 10 years, the prevailing view of the functions of cohesin in cell biology has undergone a revolutionary transformation. Initially, the predominant view of cohesin was as a ring that encircled and cohered replicated chromosomes until its cleavage triggered the metaphase-to-anaphase transition. As such, early studies focused on the role of tumour-derived cohesin mutations in the fidelity of chromosome segregation and aneuploidy. However, over the past 5 years the cohesin field has shifted dramatically, and research now focuses on the primary role of cohesin in generating, maintaining and regulating the intra-chromosomal DNA looping events that modulate 3D genome organization and gene expression. This Review focuses on recent discoveries in the cohesin field that provide insight into the role of cohesin inactivation in cancer pathogenesis, and opportunities for exploiting these findings for the clinical benefit of patients with cohesin-mutant cancers.

摘要翻译： 

人类癌症中黏连蛋白复合体的突变大约在10年前首次被发现。此后，全球研究人员证实黏连蛋白是癌症中最常发生突变的蛋白复合体之一。编码黏连蛋白亚基的基因失活突变常见于膀胱癌、儿童肉瘤、白血病、脑肿瘤及其他癌症类型。同样在这10年间，关于黏连蛋白在细胞生物学中功能的主流观点经历了革命性转变。最初，黏连蛋白主要被视为环绕并连接复制后染色体的环状结构，直至其裂解触发细胞从中期向后期的转变。因此，早期研究主要关注肿瘤源性黏连蛋白突变对染色体分离保真度及非整倍体性的影响。然而过去5年来，黏连蛋白研究领域发生显著转变，当前研究集中于黏连蛋白在生成、维持和调控染色体内DNA环化事件中的核心作用——这些事件调控三维基因组结构和基因表达。本综述重点关注黏连蛋白领域的最新发现，以揭示黏连蛋白失活在癌症发病机制中的作用，并探讨如何利用这些发现为黏连蛋白突变癌症患者提供临床获益。

原文链接：

Emerging themes in cohesin cancer biology