Calcium Wave Promotes Cell Extrusion
Calcium Wave Promotes Cell Extrusion
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DOI：
10.1016/j.cub.2019.11.089
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发表时间：
2020-02-24
期刊：
影响因子：
9.2
通讯作者：
Fujita, Yasuyuki
中科院分区：
文献类型：
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作者：
Takeuchi, Yasuto;Narumi, Rika;Fujita, Yasuyuki
当上皮内发生致癌转化或细胞凋亡时，有害或死亡的细胞从组织顶部挤出以维持上皮稳态。然而，潜在的分子机制仍然难以捉摸。在这项研究中，我们首先使用哺乳动物培养的上皮细胞和斑马鱼胚胎证明，在 RasV12 转化细胞顶端挤出之前，钙波从转化细胞中产生并传播到周围细胞。然后钙波触发并促进挤出过程。 IP3受体、间隙连接和机械敏感钙通道TRPC1参与钙波。钙波引起周围细胞向挤压转化细胞的极化运动。此外，钙波至少部分地通过诱导周围细胞中的肌动蛋白重排来促进顶端挤出。此外，类似的钙增殖也促进凋亡细胞的顶端挤出。因此，钙波是一种进化上保守的、通用的细胞挤出调节机制。
When oncogenic transformation or apoptosis occurs within epithelia, the harmful or dead cells are apically extruded from tissues to maintain epithelial homeostasis. However, the underlying molecular mechanism still remains elusive. In this study, we first show, using mammalian cultured epithelial cells and zebrafish embryos, that prior to apical extrusion of RasV12-transformed cells, calcium wave occurs from the transformed cell and propagates across the surrounding cells. The calcium wave then triggers and facilitates the process of extrusion. IP3 receptor, gap junction, and mechanosensitive calcium channel TRPC1 are involved in calcium wave. Calcium wave induces the polarized movement of the surrounding cells toward the extruding transformed cells. Furthermore, calcium wave facilitates apical extrusion, at least partly, by inducing actin rearrangement in the surrounding cells. Moreover, comparable calcium propagation also promotes apical extrusion of apoptotic cells. Thus, calcium wave is an evolutionarily conserved, general regulatory mechanism of cell extrusion.