Activation of GPER suppresses epithelial mesenchymal transition of triple negative breast cancer cells via NF-κB signals

Zhuo Jia Chen, Wei Wei, Guan Min Jiang, Hao Liu, Wei Dong Wei, Xiangling Yang, Ying Min Wu, Huanliang Liu, Chris K C WONG, Jun Du, Hong Sheng Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

The targeted therapy for triple-negative breast cancer (TNBC) is a great challenge due to our poor understanding on its molecular etiology. In the present study, our clinical data showed that the expression of G-protein coupled estrogen receptor (GPER) is negatively associated with lymph node metastasis, high-grade tumor and fibronectin (FN) expression while positively associated with the favorable outcome in 135 TNBC patients. In our experimental studies, both the in vitro migration and invasion of TNBC cells were inhibited by GPER specific agonist G-1, through the suppression of the epithelial mesenchymal transition (EMT). The G-1 treatment also reduced the phosphorylation, nuclear localization, and transcriptional activities of NF-κB. While over expression of NF-κB attenuated the action of G-1 in suppressing EMT. Our data further illustrated that the phosphorylation of GSK-3β by PI3K/Akt and ERK1/2 mediated, at least partially, the inhibitory effect of G-1 on NF-κB activities. It was further confirmed in a study of MDA-MB-231 tumor xenografts in nude mice. The data showed that G-1 inhibited the in vivo growth and invasive potential of TNBC via suppression of EMT. Our present study demonstrated that an activation of GPER pathway elicits tumor suppressive actions on TNBC, and supports the use of G-1 therapeutics for TNBC metastasis.

Original languageEnglish
Pages (from-to)775-788
Number of pages14
JournalMolecular Oncology
Volume10
Issue number6
DOIs
Publication statusPublished - 1 Jun 2016

Scopus Subject Areas

  • Molecular Medicine
  • Genetics
  • Oncology
  • Cancer Research

User-Defined Keywords

  • EMT
  • G-1
  • GPER
  • NF-κB
  • TNBC

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