Regulation of epithelial migration by epithelial cell adhesion molecule requires its Claudin-7 interaction domain.

Regulation of epithelial migration by epithelial cell adhesion molecule requires its Claudin-7 interaction domain.
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DOI:
10.1371/journal.pone.0204957
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发表时间:
2018
期刊:
影响因子:
3.7
通讯作者:
Riedel-Kruse IH
Riedel-Kruse IH
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Barth AIM;Kim H;Riedel-Kruse IH

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上皮细胞粘附分子(EpCAM)是上皮细胞表面上的糖蛋白,其对于肠上皮完整性是必需的,并且在许多上皮来源的癌症和循环肿瘤细胞中以高水平表达。在这里,我们显示了EpCAM水平对Madin-Darby-Canine Kidney(MDCK)上皮细胞迁移的影响。耗尽EpCAM的MDCK细胞显示细胞外信号调节激酶(ERK)和肌球蛋白的活化增加,并且细胞铺展和上皮片迁移到间隙中增加。相反,EpCAM的过表达抑制ERK和肌球蛋白活化,并减缓上皮片迁移。EpCAM的损失通过在顺式二聚化所需的胞外结构域中突变的EpCAM-YFP来挽救,而具有抑制紧密连接蛋白-7相互作用的突变的EpCAM-YFP不能挽救EpCAM耗尽的细胞中增加的ERK、肌球蛋白活化和增加的迁移。总之,这些结果表明EpCAM和Claudin-7在细胞表面的相互作用通过抑制ERK和肌动球蛋白收缩性来负调节上皮迁移。
Epithelial cell adhesion molecule (EpCAM) is a glycoprotein on the surface of epithelial cells that is essential for intestinal epithelial integrity and expressed at high levels in many epithelial derived cancers and circulating tumor cells. Here we show the effect of EpCAM levels on migration of Madin-Darby-Canine Kidney (MDCK) epithelial cells. MDCK cells depleted of EpCAM show increased activation of extracellular signal-regulated kinase (ERK) and of myosin, and increased cell spreading and epithelial sheet migration into a gap. In contrast, over-expression of EpCAM inhibits ERK and myosin activation, and slows epithelial sheet migration. Loss of EpCAM is rescued by EpCAM-YFP mutated in the extracellular domain required for cis-dimerization whereas EpCAM-YFP with a mutation that inhibits Claudin-7 interaction cannot rescue increased ERK, myosin activation, and increased migration in EpCAM-depleted cells. In summary, these results indicate that interaction of EpCAM and Claudin-7 at the cell surface negatively regulates epithelial migration by inhibiting ERK and actomyosin contractility.
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