The Affiliated Hospital and the Medical College, Hebei University of Engineering, Handan, Hebei Province, PR China; The Hormel Institute, University of Minnesota, Austin, MN, USA; The Shijiazhuang Second Hospital, Shijiazhuang, Hebei, PR China.
The Affiliated Hospital and the Medical College, Hebei University of Engineering, Handan, Hebei Province, PR China.
Biochem Biophys Res Commun. 2019 Aug 27;516(3):976-982. doi: 10.1016/j.bbrc.2019.06.132. Epub 2019 Jul 2.
Actin is a highly abundant cytoskeletal protein that is essential for all eukaryotic cells and participates in many structural and functional roles. It has long been noted that estrogen affects cellular morphology. However, recent studies observed that both estrogen and tamoxifen induce a remarkable cytoskeletal remodeling independent of ER. In addition to ER, G protein-coupled estrogen receptor 1 (GPER, also known as GPR30) also binds to estrogen with high affinity and mediates intracellular estrogenic signaling. Here, we show that activation of GPER by its specific agonist G-1 induces re-organization of F-actin cytoskeleton. We further demonstrate that GPER acts through PLCβ-PKC and Rho/ROCK-LIMK-Cofilin pathway, which are upstream regulators of F-actin cytoskeleton assembly, thereby enhancing TAZ nuclear localization and activation. Furthermore, we find that LIMK1/2 is critical for GPER activation-induced breast cancer cell migration. Together, our results suggest that GPER mediates G-1-induced cytoskeleton assembly and GPER promotes breast cancer cell migration via PLCβ-PKC and Rho/ROCK-LIMK-Cofilin pathway.
肌动蛋白是一种高度丰富的细胞骨架蛋白，对所有真核细胞都是必不可少的，参与许多结构和功能角色。长期以来，人们一直注意到雌激素会影响细胞形态。然而，最近的研究观察到，雌激素和他莫昔芬都能独立于 ER 诱导显著的细胞骨架重塑。除了 ER，G 蛋白偶联雌激素受体 1（GPER，也称为 GPR30）也能与雌激素高亲和力结合，并介导细胞内雌激素信号。在这里，我们表明其特异性激动剂 G-1 激活 GPER 诱导 F-肌动蛋白细胞骨架的重新组织。我们进一步证明，GPER 通过 PLCβ-PKC 和 Rho/ROCK-LIMK-Cofilin 途径发挥作用，该途径是 F-肌动蛋白细胞骨架组装的上游调节剂，从而增强 TAZ 的核定位和激活。此外，我们发现 LIMK1/2 对 GPER 激活诱导的乳腺癌细胞迁移至关重要。总之，我们的结果表明，GPER 介导 G-1 诱导的细胞骨架组装，GPER 通过 PLCβ-PKC 和 Rho/ROCK-LIMK-Cofilin 途径促进乳腺癌细胞迁移。
