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有丝分裂错误对细胞增殖和肿瘤发生的影响。

The impact of mitotic errors on cell proliferation and tumorigenesis.

机构信息

Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.

出版信息

Genes Dev. 2018 May 1;32(9-10):620-638. doi: 10.1101/gad.314351.118.

Abstract

Mitosis is a delicate event that must be executed with high fidelity to ensure genomic stability. Recent work has provided insight into how mitotic errors shape cancer genomes by driving both numerical and structural alterations in chromosomes that contribute to tumor initiation and progression. Here, we review the sources of mitotic errors in human tumors and their effect on cell fitness and transformation. We discuss new findings that suggest that chromosome missegregation can produce a proinflammatory environment and impact tumor responsiveness to immunotherapy. Finally, we survey the vulnerabilities exposed by cell division errors and how they can be exploited therapeutically.

摘要

有丝分裂是一个精细的事件,必须高度保真地执行,以确保基因组的稳定性。最近的工作提供了深入的了解,即有丝分裂错误如何通过驱动染色体的数量和结构改变来塑造癌症基因组,从而促进肿瘤的发生和发展。在这里,我们回顾了人类肿瘤中有丝分裂错误的来源及其对细胞适应性和转化的影响。我们讨论了新的发现,表明染色体错误分离可以产生促炎环境,并影响肿瘤对免疫治疗的反应。最后,我们调查了细胞分裂错误暴露的脆弱性以及如何在治疗上加以利用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc5d/6004076/008004c16b0f/620f01.jpg

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