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复制压力通过挤压促进细胞消除
2021-05-07 16:16

美国麻省理工学院H. Robert Horvitz研究组发现,复制压力通过挤出促进细胞消除。2021年5月5日,国际知名学术期刊《自然》在线发表了这一成果。

为了分析秀丽隐杆线虫胚胎的细胞挤压,研究人员进行了全基因组的RNA干扰筛选,鉴定了多个具有S期特异性功能的细胞周期基因,并进行了实时成像实验,从而确定这些基因如何控制挤压。挤压细胞在S期经历复制压力,并通过ATR和CHK1的同源物激活复制压力反应。阻止S期进入,抑制复制应激反应或完成细胞周期可阻止细胞挤压。羟基脲诱导的复制应激触发了ATR–CHK1和p53依赖性细胞从哺乳动物上皮单层挤压。研究人员认为,复制应激诱导的细胞挤压在动物之间是保守的,并提出该挤压过程是哺乳动物体内细胞消除的主要机制,并具有肿瘤抑制功能。

据介绍,细胞挤压是一种细胞消除的机制,被海绵、线虫、昆虫和哺乳动物等各种生物所使用。在挤压过程中,一个小室会从周围的小室层中分离出来,同时保持该层的连续性。脊椎动物的上皮组织主要通过挤压消除细胞,并且细胞挤压失调与包括癌症在内的上皮疾病有关。目前尚未完全了解驱动细胞挤压的机制。

附:英文原文

Title: Replication stress promotes cell elimination by extrusion

Author: Vivek K. Dwivedi, Carlos Pardo-Pastor, Rita Droste, Ji Na Kong, Nolan Tucker, Daniel P. Denning, Jody Rosenblatt, H. Robert Horvitz

Issue&Volume: 2021-05-05

Abstract: Cell extrusion is a mechanism of cell elimination that is used by organisms as diverse as sponges, nematodes, insects and mammals1,2,3. During extrusion, a cell detaches from a layer of surrounding cells while maintaining the continuity of that layer4. Vertebrate epithelial tissues primarily eliminate cells by extrusion, and the dysregulation of cell extrusion has been linked to epithelial diseases, including cancer1,5. The mechanisms that drive cell extrusion remain incompletely understood. Here, to analyse cell extrusion by Caenorhabditis elegans embryos3, we conducted a genome-wide RNA interference screen, identified multiple cell-cycle genes with S-phase-specific function, and performed live-imaging experiments to establish how those genes control extrusion. Extruding cells experience replication stress during S phase and activate a replication-stress response via homologues of ATR and CHK1. Preventing S-phase entry, inhibiting the replication-stress response, or allowing completion of the cell cycle blocked cell extrusion. Hydroxyurea-induced replication stress6,7 triggered ATR–CHK1- and p53-dependent cell extrusion from a mammalian epithelial monolayer. We conclude that cell extrusion induced by replication stress is conserved among animals and propose that this extrusion process is a primordial mechanism of cell elimination with a tumour-suppressive function in mammals.

DOI: 10.1038/s41586-021-03526-y

Source: https://www.nature.com/articles/s41586-021-03526-y

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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