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

Zhen Wang, Li Sun, Shuang Liang, Zan chao Liu, Zeng yi Zhao, Jie Yang, Defeng Wang, DaQing Yang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)976-982
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume516
Issue number3
DOIs
StatePublished - Aug 27 2019

Bibliographical note

Funding Information:
Funding: This work was supported by Hebei Natural Science Foundation Youth Fund ( C2019402141 ); Science and Technology Research Project of Hebei Education Department ( QN2019215 ); Innovation fund project of Hebei University of Engineering ( SJ010002098 ); Handan Science and Technology Research and Development Plan ( 1727201061 ); Hebei Cultivation of excellent clinical medical talents and basic research Projects ( 361037 ); and a Paint-The-Town-Pink (PTTP) Research Grant from The Hormel Institute of the University of Minnesota .

Keywords

  • Breast cancer
  • F-actin cytoskeleton
  • GPER
  • TAZ

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