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扩增的中心体——不仅仅是威胁。

Amplified centrosomes-more than just a threat.

机构信息

Life and Medical Sciences Institute, Immune and Tumor Biology, University of Bonn, Bonn, Germany.

Institute for Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.

出版信息

EMBO Rep. 2024 Oct;25(10):4153-4167. doi: 10.1038/s44319-024-00260-0. Epub 2024 Sep 16.

Abstract

Centrosomes are major organizing components of the tubulin-based cytoskeleton. In recent years, we have gained extensive knowledge about their structure, biogenesis, and function from single cells, cell-cell interactions to tissue homeostasis, including their role in human diseases. Centrosome abnormalities are linked to, among others primary microcephaly, birth defects, ciliopathies, and tumorigenesis. Centrosome amplification, a state where two or more centrosomes are present in the G1 phase of the cell cycle, correlates in cancer with karyotype alterations, clinical aggressiveness, and lymph node metastasis. However, amplified centrosomes also appear in healthy tissues and, independent of their established role, in multi-ciliation. One example is the liver where hepatocytes carry amplified centrosomes owing to whole-genome duplication events during organogenesis. More recently, amplified centrosomes have been found in neuronal progenitors and several cell types of hematopoietic origin in which they enhance cellular effector functions. These findings suggest that extra centrosomes do not necessarily pose a risk for genome integrity and are harnessed for physiological processes. Here, we compare established and emerging 'non-canonical functions' of amplified centrosomes in cancerous and somatic cells and discuss their role in cellular physiology.

摘要

中心体是微管细胞骨架的主要组成部分。近年来,我们从单细胞、细胞间相互作用到组织稳态等方面,对中心体的结构、发生和功能有了广泛的了解,包括其在人类疾病中的作用。中心体异常与原发性小头畸形、出生缺陷、纤毛病和肿瘤发生等有关。中心体扩增是指在细胞周期的 G1 期存在两个或更多中心体的状态,它与癌症中的核型改变、临床侵袭性和淋巴结转移相关。然而,扩增的中心体也出现在健康组织中,并且独立于其已确立的作用,出现在多纤毛中。一个例子是肝脏,在那里,由于器官发生过程中的全基因组复制事件,肝细胞携带扩增的中心体。最近,在神经元祖细胞和造血来源的几种细胞类型中也发现了扩增的中心体,它们增强了细胞的效应功能。这些发现表明,额外的中心体不一定对基因组完整性构成风险,而是被用于生理过程。在这里,我们比较了扩增的中心体在癌细胞和体细胞中的已确立和新兴的“非典型功能”,并讨论了它们在细胞生理学中的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dd8/11467336/d465da4d49d1/44319_2024_260_Fig1_HTML.jpg

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