A novel role for p115RhoGEF in regulation of epithelial plasticity.
A novel role for p115RhoGEF in regulation of epithelial plasticity.
复制标题
DOI：
10.1371/journal.pone.0085409
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Worthylake RA
中科院分区：
文献类型：
--
作者：
Kher SS;Struckhoff AP;Alberts AS;Worthylake RA
上皮可塑性在伤口愈合和组织再生等生理过程中起着至关重要的作用，上皮可塑性失调可导致癌症等病理状况。细胞-细胞连接是上皮细胞的一个关键特征，连接的丧失与间充质特征的获得有关，例如增强的突出和迁移。尽管 Rho 与上皮细胞连接的调节有关，但 Rho 信号在上皮可塑性调节中的作用尚不清楚。我们发现 RGS RhoGEFs 家族的成员在乳腺上皮细胞的上皮细胞-细胞连接的调节中发挥着关键作用。我们确定了 p115RhoGEF 在调节上皮可塑性中的新作用。 p115RhoGEF 的缺失导致连接 E-钙粘蛋白减少，突出性和迁移性增强。相反，p115RhoGEF 的过度表达增强了连接 E-钙粘蛋白并抑制细胞突出和迁移。 23 个 Rho 效应子的 siRNA 筛选表明，透明相关福明 (DRF) 家族的成员是 p115RhoGEF 介导的上皮可塑性变化所必需的。因此，我们的数据表明 p115RhoGEF 在上皮可塑性调节中的新作用，这依赖于 Rho-DRF 信号模块。
Epithelial plasticity plays a critical role during physiological processes, such as wound healing and tissue regeneration, and dysregulation of epithelial plasticity can lead to pathological conditions, such as cancer. Cell-cell junctions are a critical feature of epithelial cells and loss of junctions is associated with acquisition of mesenchymal features, such as enhanced protrusion and migration. Although Rho has been implicated in regulation of junctions in epithelial cells, the role of Rho signaling in the regulation of epithelial plasticity has not been understood. We show that members of the RGS RhoGEFs family play a critical role in regulation of epithelial cell-cell junctions in breast epithelial cells. We identify a novel role for p115RhoGEF in regulation of epithelial plasticity. Loss of p115RhoGEF leads to decreased junctional E-cadherin and enhanced protrusiveness and migration. Conversely, overexpression of p115RhoGEF enhanced junctional E-cadherin and inhibited cell protrusion and migration. siRNA screen of 23 Rho effectors showed that members of the Diaphanous-Related Formin (DRF) family are required for p115RhoGEF-mediated changes in epithelial plasticity. Thus, our data indicates a novel role for p115RhoGEF in regulation of epithelial plasticity, which is dependent on Rho-DRF signaling module.
登录
查看更多内容
影响因子：
82.9
作者：
Guilluy, Christophe;Bregeon, Jeremy;Loirand, Gervaise
通讯作者：
Loirand, Gervaise
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
21.3
作者：
Levayer, Romain;Pelissier-Monier, Anne;Lecuit, Thomas
通讯作者：
Lecuit, Thomas
影响因子：
9.2
作者：
Bravo-Cordero, Jose Javier;Oser, Matthew;Chen, Xiaoming;Eddy, Robert;Hodgson, Louis;Condeelis, John
通讯作者：
Condeelis, John
影响因子：
64.8
作者：
Pertz, O;Hodgson, L;Hahn, KM
通讯作者：
Hahn, KM