中心体
有丝分裂
主轴检查点
染色体不稳定性
癌变
多极纺锤
生物
细胞生物学
癌症研究
PLK1
极光抑制剂
细胞周期
染色体分离
端粒酶
细胞分裂
癌症
主轴装置
细胞
遗传学
染色体
基因
出处
期刊:PubMed
[National Institutes of Health]
日期:2017-06-20
卷期号:25 (6): 477-480
标识
DOI:10.3760/cma.j.issn.1007-3418.2017.06.019
摘要
Aurora A plays a key role in cellular mitosis. It is located in the centrosome and spindle, and is mainly involved in the processes of centrosome maturation and separation, bipolar spindle assembly, and the regulation of mitotic progression. Recent studies have suggested that Aurora A is involved in tumorigenesis and tumor development through multiple mechanisms. Overexpression of Aurora A could cause abnormal centrosome amplification, aneuploidy formation, and G2/M checkpoint defects, which result in chromosome instability and imbalance between cell division and apoptosis, and eventually leads to abnormal cell proliferation. Aurora A also participates in the regulation of the p53 and BRCA1 pathways, leading to suppressor gene dysfunction and changes in cell viability, and it induces telomerase activity by upregulating c-Myc, resulting in tumorigenesis. In addition, Aurora A also induces drug resistance in liver cancer cells. Thus, Aurora A has gradually become a new target for cancer therapy in recent years. This paper has summarized the recent studies on Aurora A, and reviewed its biological functions in cell mitosis and roles in liver tumorigenesis.Aurora A在细胞有丝分裂过程中发挥重要作用,它位于中心体和纺锤体,主要参与中心体的成熟和分离、双极纺锤体的组装,以及有丝分裂进程的调控。近年发现Aurora A可通过多种机制参与肿瘤的发生及发展。Aurora A过表达可引起中心体异常扩增和异倍体形成、纺锤体检查点缺陷和染色体不稳定,导致细胞凋亡和有丝分裂间的平衡失调,引起细胞异常增殖;Aurora A还参与p53、BRCA1通路的调节,导致这些抑癌基因功能障碍和细胞活力变化,并通过上调c-Myc诱导端粒酶活性,引起肝癌发生。Aurora A还可诱导肝癌细胞耐药性。因此,近年它逐渐成为肿瘤治疗的一个新靶点。现总结近年针对Aurora A激酶的研究,对其生物学功能及其在肝癌发生中的作用进行综述。.
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