Department of Bioengineering, Stanford University, Stanford, CA, United States of America.
PLoS One. 2018 Oct 10;13(10):e0204957. doi: 10.1371/journal.pone.0204957. eCollection 2018.
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.
上皮细胞黏附分子（EpCAM）是一种位于上皮细胞表面的糖蛋白，对于肠道上皮细胞的完整性至关重要，并且在许多上皮来源的癌症和循环肿瘤细胞中高表达。在这里，我们展示了 EpCAM 水平对 Madin-Darby-Canine Kidney（MDCK）上皮细胞迁移的影响。EpCAM 耗尽的 MDCK 细胞显示出细胞外信号调节激酶（ERK）和肌球蛋白的激活增加，细胞铺展和上皮片层迁移到间隙中增加。相比之下，EpCAM 的过表达抑制 ERK 和肌球蛋白的激活，并减缓上皮片层的迁移。EpCAM-YFP 突变体在细胞外结构域中缺失 cis-二聚化所必需的突变体可以挽救 EpCAM 耗尽细胞中 ERK、肌球蛋白激活和迁移增加，而抑制 Claudin-7 相互作用的 EpCAM-YFP 突变体则不能挽救。总之，这些结果表明，细胞表面上的 EpCAM 和 Claudin-7 的相互作用通过抑制 ERK 和肌球蛋白收缩性来负调控上皮细胞迁移。
