SCI
19 June
Emerging themes in cohesin cancer biology
Waldman Todd,Emerging themes in cohesin cancer biology.[J] .Nat. Rev. Cancer, , undefined: undefined.
Abstract 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.
人类癌症中黏连蛋白复合物的突变大约在前首次被发现。从那时起，世界各地的研究人员已经证明黏连蛋白是癌症中最常见的突变蛋白复合物之一。编码黏连蛋白亚基的基因失活突变在膀胱癌、儿科肉瘤、白血病、脑瘤和其他类型的癌症中很常见。同样在这里，细胞生物学中关于黏连蛋白功能的主流观点发生了革命性的转变。最初，黏连蛋白的主要观点是一个环绕和黏连复制的染色体的环状物，直到它的分裂触发中期到后期的转变。因此，早期的研究集中于肿瘤源黏连蛋白突变在染色体分离保真度和非整倍体中的作用。然而，在过去的5年里，黏连蛋白领域发生了巨大的变化，目前的研究重点集中在黏连蛋白在产生、维持和调节染色体内DNA循环事件(调节3D基因组组织和基因表达)中的主要作用。本文综述了黏连蛋白领域的最新发现，这些发现为黏连蛋白失活在癌症发病机制中的作用提供了深入了解，并为利用这些发现为黏连蛋白突变癌症患者的临床治疗提供了机会。
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