Translocation of LSR from tricellular corners causes macropinocytosis at cell?cell interface as a trigger for breaking out of contact inhibition
Translocation of LSR from tricellular corners causes macropinocytosis at cell?cell interface as a trigger for breaking out of contact inhibition
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LSR 从三细胞角的易位导致细胞-细胞界面的巨胞饮作用，作为突破接触抑制的触发因素
DOI：
10.1096/fj.202100299r
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Kojima Takashi
中科院分区：
文献类型：
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作者：
Kohno Takayuki;Konno Takumi;Kikuchi Shin;Kondoh Masuo;Kojima Takashi
退出接触抑制对于上皮癌前体细胞启动细胞生长和运动是必要的。然而，人们对静态条件下细胞突然开始生长的机制知之甚少。我们将重点放在细胞连接处，作为打破接触抑制的区域之一。在分化良好的子宫内膜癌细胞中，Sawano 给予三细胞紧密连接蛋白 LSR 的配体，短暂地降低了稳健的连接特性，导致细胞运动性突然增加，从而导致细胞过度生长，尽管处于接触抑制条件下。我们观察到，巨胞饮作用基本上和暂时地作为上述过程的先行事件发生在细胞间连接处，而没有破坏连接装置，但不在顶端质膜处发生。总的来说，我们得出的结论是，源自紧密连接介导的信号传导的巨胞饮作用的形成是由静态癌前上皮中细胞生长的启动而触发的。
Withdrawal from contact inhibition is necessary for epithelial cancer precursor cells to initiate cell growth and motility. Nevertheless, little is understood about the mechanism for the sudden initiation of cell growth under static conditions. We focused on cellular junctions as one region where breaking out of contact inhibition occurs. In well‐differentiated endometrial cancer cells, Sawano, the ligand administration for tricellular tight junction protein LSR, which transiently decreased the robust junction property, caused an abrupt increase in cell motility and consequent excessive multilayered cell growth despite being under contact inhibition conditions. We observed that macropinocytosis essentially and temporarily occurred as an antecedent event for the above process at intercellular junctions without disruption of the junction apparatus but not at the apical plasma membrane. Collectively, we concluded that the formation of macropinocytosis, which is derived from tight junction‐mediated signaling, was triggered for the initiation of cell growth in static precancerous epithelium.