文章：

中心体畸变：癌症进展的原因还是结果？

Centrosome aberrations: cause or consequence of cancer progression?

原文发布日期：2002-11-01

DOI: 10.1038/nrc924

类型: Review Article

开放获取: 否

要点：

1. The centrosome nucleates microtubules; it is important for cell shape, motility and division. During S phase of the cell cycle, the single centrosome that is present in a G1-phase cell is duplicated. The two centrosomes then set up the poles of the mitotic spindle and each incipient daughter cell receives one centrosome.
2. The duplication and segregation cycles of centrosomes and chromosomes need to be coordinated to avoid chromosome missegregation or ploidy changes. The retinoblastoma pathway has been identified as one important link between centrosome duplication and chromosome replication.
3. Many tumours display numerical and structural centrosome aberrations. Extra copies of centrosomes could, in principle, arise through overduplication within a single cell cycle, through aborted cell division, cell fusion or de novo genesis. A growing body of evidence points to aborted division as an important cause of excessive centrosome numbers.
4. Cells that lack a functional p53 pathway are proposed to acquire multiple centrosomes through failure of a G1-phase checkpoint that should eliminate cells after aborted division. However, it has also been argued that p53 regulates centrosome duplication.
5. Centrosome aberrations can give rise to chromosomal instability and altered tissue architecture. Importantly, centrosome aberrations and chromosomal instability are expected to enhance each other.
6. Most multipolar divisions cause severe chromosome missegregation and therefore constitute lethal events. Occasionally, however, they might give rise to cells with chromosomal compositions that favour survival in the microenvironment of the tumour. In tumour cells, genes that are involved in alternative mechanisms for spindle formation might be upregulated or re-expressed. This might cause several centrosomes to coalesce and allow the formation of bipolar spindles, in spite of excessive centrosome numbers.
7. A better understanding of the origins and consequences of centrosome aberrations could lead to the development of novel diagnostic, prognostic or therapeutic approaches.

要点翻译：

1. 中心体负责 nucleates 微管，对细胞形态、运动性和分裂至关重要。在细胞周期的 S 期，G1 期细胞中存在的单个中心体会发生复制。随后，两个中心体形成有丝分裂纺锤体的两极，每个新生子细胞各获得一个中心体。
2. 中心体与染色体的复制和分离周期需要协调一致，以避免染色体错误分离或倍性改变。视网膜母细胞瘤通路已被确定为连接中心体复制与染色体复制的重要桥梁。
3. 许多肿瘤存在中心体数量异常和结构畸变。中心体的额外拷贝可能源于单个细胞周期内的过度复制、细胞分裂失败、细胞融合或从头生成。越来越多证据表明，分裂失败是中心体数量过多的主要原因。
4. 缺乏功能性 p53 通路的细胞可能因 G1 期检查点失效（该检查点本应在分裂失败后清除异常细胞）而获得多个中心体。但也有研究认为 p53 直接调控中心体复制。
5. 中心体异常可导致染色体不稳定性和组织架构改变。值得注意的是，中心体异常与染色体不稳定预期会形成相互增强的恶性循环。
6. 多数多极分裂会导致严重染色体错误分离，因而构成致死事件。但偶尔也可能产生染色体组合更适应肿瘤微环境生存的细胞。在肿瘤细胞中，参与纺锤体形成替代机制的基因可能被上调或重新表达——这可能导致多个中心体聚集成簇，从而在中心体超量的情况下仍形成双极纺锤体。
7. 更好理解中心体异常的起源与后果，或将推动新型诊断、预后判断及治疗方法的开发。

英文摘要：

Many human tumours show centrosome aberrations, indicating an underlying deregulation of centrosome structure, duplication or segregation. Centrosomes organize microtubule arrays throughout the cell cycle, thereby influencing both tissue architecture and the accuracy of chromosome segregation. But what are the origins of centrosomal abnormalities in tumours, and what impact do they have on the generation of invasive, genetically unbalanced cells during cancer progression?

摘要翻译： 

许多人类肿瘤表现出中心体异常，提示其存在中心体结构、复制或分离的失调。中心体在整个细胞周期中组织微管阵列，从而影响组织结构及染色体分离的准确性。然而，肿瘤中中心体异常的起源是什么？它们又在癌症进展过程中，对具有侵袭性、遗传失衡的细胞的产生产生了怎样的影响？

原文链接：

Centrosome aberrations: cause or consequence of cancer progression?