Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis
Extracellular ATP facilitates cell extrusion from epithelial layers mediated by cell competition or apoptosis
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细胞外 ATP 通过细胞竞争或细胞凋亡促进细胞从上皮层挤出
DOI：
10.1016/j.cub.2022.03.057
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发表时间：
2022
期刊：
影响因子：
9.2
通讯作者：
Fujita Yasuyuki
中科院分区：
文献类型：
--
作者：
Mori Yusuke;Shiratsuchi Naoka;Sato Nanami;Chaya Azusa;Tanimura Nobuyuki;Ishikawa Susumu;Kato Mugihiko;Kameda Ikumi;Kon Shunsuke;Haraoka Yukinari;Ishitani Tohru;Fujita Yasuyuki
为了维持上皮内环境稳定，各种异常或功能障碍的细胞被积极地从上皮层中清除。这种细胞挤出过程主要福尔斯两种模式：细胞竞争介导的挤出和凋亡挤出。然而，目前还不清楚这些过程是否以及如何由共同的分子机制控制。在这项研究中，我们证明了活性氧（ROS）水平升高，在广泛的上皮层周围挤压转化或凋亡细胞。ROS的下调抑制了挤出过程。此外，ATP从挤压细胞中分泌到细胞外，这促进了ROS水平和细胞挤压。此外，细胞外ATP和ROS途径积极调节周围细胞的极化运动，在细胞竞争介导的和凋亡的挤压挤压细胞。因此，细胞外ATP充当“挤出我”信号，并且在细胞挤出中起主要作用，从而维持上皮稳态并预防病理状况或病症。
For the maintenance of epithelial homeostasis, various aberrant or dysfunctional cells are actively eliminated from epithelial layers. This cell extrusion process mainly falls into two modes: cell-competition-mediated extrusion and apoptotic extrusion. However, it is not clearly understood whether and how these processes are governed by common molecular mechanisms. In this study, we demonstrate that the reactive oxygen species (ROS) levels are elevated within a wide range of epithelial layers around extruding transformed or apoptotic cells. The downregulation of ROS suppresses the extrusion process. Furthermore, ATP is extracellularly secreted from extruding cells, which promotes the ROS level and cell extrusion. Moreover, the extracellular ATP and ROS pathways positively regulate the polarized movements of surrounding cells toward extruding cells in both cell-competition-mediated and apoptotic extrusion. Hence, extracellular ATP acts as an "extrude me" signal and plays a prevalent role in cell extrusion, thereby sustaining epithelial homeostasis and preventing pathological conditions or disorders.
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