Accumulation of the myosin-II-spectrin complex plays a positive role in apical extrusion of Src-transformed epithelial cells
Accumulation of the myosin-II-spectrin complex plays a positive role in apical extrusion of Src-transformed epithelial cells
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肌球蛋白-II-血影蛋白复合物的积累在 Src 转化的上皮细胞的顶端挤出中发挥积极作用
DOI：
10.1111/gtc.12643
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发表时间：
2018
期刊：
影响因子：
2.1
通讯作者：
Yasuyuki Fujita
中科院分区：
文献类型：
--
作者：
Mikio Takagi;Masaya Ikegawa;Takashi Shimada;Susumu Ishikawa;Mihoko Kajita;Takeshi Maruyama;Tomoko Kamasaki;Yasuyuki Fujita
在癌变的初始阶段，转化发生在上皮内的单个细胞中。最近的研究表明，新出现的转化细胞往往是从上皮组织的顶端消除。然而，这种癌症预防现象的潜在分子机制仍然难以捉摸。在这项研究中，我们首先证明了肌球蛋白II在Src转化细胞中积累，当它们被正常上皮细胞包围时。敲低肌球蛋白-II的重链实质上减少Src细胞的顶端挤出，表明积累的肌球蛋白-II正调控转化细胞的顶端消除。此外，我们在正常和Src转化的上皮细胞共培养下鉴定出β血影蛋白是一种肌球蛋白II结合蛋白。β血影蛋白也在被正常细胞包围的Src细胞中积累，β血影蛋白积累受肌球蛋白II调节。此外，β血影蛋白的敲低显著抑制Src细胞的顶端挤出。总的来说，这些结果表明肌球蛋白-II-血影蛋白复合物的积累在Src转化的上皮细胞的顶端挤出中起积极作用。进一步阐明根尖挤压的分子机制将有助于建立一种新型的癌症预防药物。
At the initial stage of carcinogenesis, transformation occurs in single cells within the epithelium. Recent studies have revealed that the newly emerging transformed cells are often apically eliminated from epithelial tissues. However, the underlying molecular mechanisms of this cancer preventive phenomenon still remain elusive. In this study, we first demonstrate that myosin‐II accumulates in Src‐transformed cells when they are surrounded by normal epithelial cells. Knock‐down of the heavy chains of myosin‐II substantially diminishes apical extrusion of Src cells, suggesting that accumulated myosin‐II positively regulates the apical elimination of transformed cells. Furthermore, we have identified β‐spectrin as a myosin‐II‐binding protein under the coculture of normal and Src‐transformed epithelial cells. β‐spectrin is also accumulated in Src cells that are surrounded by normal cells, and the β‐spectrin accumulation is regulated by myosin‐II. Moreover, knock‐down of β‐spectrin significantly suppresses apical extrusion of Src cells. Collectively, these results indicate that accumulation of the myosin‐II‐spectrin complex plays a positive role in apical extrusion of Src‐transformed epithelial cells. Further elucidation of the molecular mechanisms of apical extrusion would lead to the establishment of a novel type of cancer preventive medicine.