《Nature》封面:癌细胞的显著特征

【字体: www.ebiotrade.com 时间:2009年07月10日 来源:生物通

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  生物通报道,哈佛医学院细胞生物学系,Dana-Farber癌症研究所,肿瘤学系,霍华休斯医学研究所的科研人员在最近的Nature上发表肿瘤研究的最新进展,A mechanism linking extra centrosomes to chromosomal instability,为本期Nature杂志的封面文章。

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生物通报道,哈佛医学院细胞生物学系,Dana-Farber癌症研究所,肿瘤学系,霍华休斯医学研究所的科研人员在最近的Nature上发表肿瘤研究的最新进展,A mechanism linking extra centrosomes to chromosomal instability,为本期Nature杂志的封面文章。

 

通讯作者David Pellman是哈佛大学医学院的教授,主要从事肿瘤细胞生物学方面的研究。

 

一直以来,科学家们认为肿瘤细胞的一个显著的特征是染色体不稳定(Chromosomal instabilityCIN),肿瘤细胞中的染色体数量或增加或减少,并且这种变化的速度比正常的细胞快很多。

 

关于CIN的机制一直都是个有争议的话题,人们长期所持的一个观点是,额外的中心体(它们与CIN有关联性)通过诱导混乱的多极纺锤体组装和非对称的细胞分裂来促使染色体错误分离。

 

图上所示微管为红色,中心体为绿色,染色体为白色

 

但是David Pellman等人发现长期活细胞成像显示,CIN癌细胞很少经历多极分裂,而且甚至当它们经历这种分裂的时候,所产生的也主要是无法生存的后代。相反,额外中心体癌细胞仅仅是经过一个过渡性的多极纺锤体阶段,在这个阶段,“异常动粒微管附着体”会积累。很多附着错误即使在额外中心体聚集形成正确双极纺锤体之后仍存在,从而增加染色体错误分离的可能性。本期封面所示为具有额外中心体的一个人细胞中的一个过渡性多极纺锤体中间形态。

(生物通 小茜)

生物通推荐原文检索:

A mechanism linking extra centrosomes to chromosomal instability

 

Neil J. Ganem1, Susana A. Godinho1 & David Pellman1

 

Howard Hughes Medical Institute, Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA

 

Abstract

Chromosomal instability (CIN) is a hallmark of many tumours and correlates with the presence of extra centrosomes1, 2, 3, 4. However, a direct mechanistic link between extra centrosomes and CIN has not been established. It has been proposed that extra centrosomes generate CIN by promoting multipolar anaphase, a highly abnormal division that produces three or more aneuploid daughter cells. Here we use long-term live-cell imaging to demonstrate that cells with multiple centrosomes rarely undergo multipolar cell divisions, and the progeny of these divisions are typically inviable. Thus, multipolar divisions cannot explain observed rates of CIN. In contrast, we observe that CIN cells with extra centrosomes routinely undergo bipolar cell divisions, but display a significantly increased frequency of lagging chromosomes during anaphase. To define the mechanism underlying this mitotic defect, we generated cells that differ only in their centrosome number. We demonstrate that extra centrosomes alone are sufficient to promote chromosome missegregation during bipolar cell division. These segregation errors are a consequence of cells passing through a transient 'multipolar spindle intermediate' in which merotelic kinetochore–microtubule attachment errors accumulate before centrosome clustering and anaphase. These findings provide a direct mechanistic link between extra centrosomes and CIN, two common characteristics of solid tumours. We propose that this mechanism may be a common underlying cause of CIN in human cancer.

 

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