GPER stabilizes F-actin cytoskeleton and activates TAZ via PLCβ-PKC and Rho/ROCK-LIMK-Cofilin pathway

Biochem Biophys Res Commun. 2019 Aug 27;516(3):976-982. doi: 10.1016/j.bbrc.2019.06.132. Epub 2019 Jul 2.

Abstract

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.

Keywords: Breast cancer; F-actin cytoskeleton; GPER; TAZ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / metabolism*
  • Actin Cytoskeleton / ultrastructure
  • Actin Depolymerizing Factors / genetics
  • Actin Depolymerizing Factors / metabolism
  • Actins / genetics*
  • Actins / metabolism
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cyclopentanes / pharmacology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lim Kinases / antagonists & inhibitors
  • Lim Kinases / genetics*
  • Lim Kinases / metabolism
  • Mammary Glands, Human / metabolism
  • Mammary Glands, Human / pathology
  • Phospholipase C beta / genetics
  • Phospholipase C beta / metabolism
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Quinolines / pharmacology
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism

Substances

  • 1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone
  • Actin Depolymerizing Factors
  • Actins
  • Cyclopentanes
  • GPER1 protein, human
  • Quinolines
  • RNA, Small Interfering
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Trans-Activators
  • Transcriptional Coactivator with PDZ-Binding Motif Proteins
  • WWTR1 protein, human
  • LIMK1 protein, human
  • LIMK2 protein, human
  • Lim Kinases
  • rho-Associated Kinases
  • Protein Kinase C
  • Phospholipase C beta