Differential actions of estrogen and SERMs in regulation of the actin cytoskeleton of endometrial cells
Differential actions of estrogen and SERMs in regulation of the actin cytoskeleton of endometrial cells
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DOI：
10.1093/molehr/gap045
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发表时间：
2009-10-01
影响因子：
4
通讯作者：
Simoncini, T.
中科院分区：
文献类型：
--
作者：
Flamini, M. I.;Sanchez, A. M.;Simoncini, T.
雌激素和选择性雌激素受体调节剂（SERM）对子宫内膜细胞功能的影响不同，然而，这些差异的生物学基础尚未建立。细胞与细胞外基质的粘附失调、细胞运动和侵袭与子宫内膜疾病如子宫内膜异位症或子宫内膜癌有关。肌动蛋白细胞骨架的重塑是实现细胞粘附和运动所必需的。雌激素受体（ER）通过核外信号级联调节肌动蛋白和细胞膜重塑。在这篇文章中，我们表明，管理的17 β-雌二醇（E2）和他莫昔芬（TAM）永生化的石川子宫内膜细胞或人子宫内膜间质细胞（ESC）的肌动蛋白纤维和细胞膜的重塑的结果。这与肌动蛋白结合蛋白膜突蛋白的Thr（558）上的快速磷酸化以及正常和石川细胞的迁移和侵袭增强有关。雷洛昔芬（RAL）不会导致膜突蛋白激活或肌动蛋白重塑。当子宫内膜细胞暴露于E2在TAM或RAL的存在下，两个SERM干扰膜突蛋白的招募，与细胞骨架的重塑，并与E2诱导的细胞运动和迁移。E2、TAM和RAL的不同作用与ER至G蛋白的核外信号传导的不同调节以及Rho相关激酶有关。这些发现增加了我们对雌激素和SERM在子宫内膜细胞中的作用的理解，并突出了潜在的分子靶点，以干扰子宫内膜疾病中遇到的雌激素相关的细胞粘附改变。
Estrogen and selective estrogen receptor modulators (SERMs) differentially impact endometrial cell function, however, the biological basis of these differences is not established. Deregulated cell adhesion to the extracellular matrix, cell movement and invasion are related to endometrial disorders, such as endometriosis or endometrial cancer. Remodeling of the actin cytoskeleton is required to achieve cell adhesion and movement. Estrogen receptor (ER) regulates actin and cell membrane remodeling through extra-nuclear signaling cascades. In this article, we show that administration of 17 beta-estradiol (E2) and tamoxifen (TAM) to immortalized Ishikawa endometrial cells or to human endometrial stromal cells (ESC) results in remodeling of actin fibers and cell membrane. This is linked to rapid phosphorylation on Thr(558) of the actin-binding protein moesin and enhanced migration and invasion of normal and Ishikawa cells. Raloxifene (RAL) does not result in moesin activation or actin remodeling. When endometrial cells are exposed to E2 in the presence of TAM or RAL, both SERMs interfere with the recruitment of moesin, with the remodeling of the cytoskeleton, and with cell movement and migration induced by E2. The differential actions of E2, TAM and RAL are linked to a distinct modulation of the extra-nuclear signaling of ER to G proteins and to the Rho-associated kinase. These findings increase our understanding of the actions of estrogen and SERMs in endometrial cells and highlight potential molecular targets to interfere with the estrogen-related altered cell adhesion encountered in endometrial disorders.