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

Autor: Ying Min Wu, Hong-Sheng Wang, Jun Du, Guan Min Jiang, Xiangling Yang, Zhuo Jia Chen, Huanliang Liu, Wei Wei, Chris K C Wong, Hao Liu, Wei Dong Wei
Rok vydání: 2016
Předmět:
0301 basic medicine
Cancer Research
medicine.medical_specialty
Epithelial-Mesenchymal Transition
MAP Kinase Signaling System
Mice
Nude
Estrogen receptor
Triple Negative Breast Neoplasms
Biology
Receptors
G-Protein-Coupled
Metastasis
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Cell Movement
Cell Line
Tumor
Internal medicine
Genetics
medicine
Animals
Humans
Breast
Epithelial–mesenchymal transition
Phosphorylation
Protein kinase B
Triple-negative breast cancer
PI3K/AKT/mTOR pathway
Glycogen Synthase Kinase 3 beta
NF-kappa B
Articles
General Medicine
Middle Aged
medicine.disease
Fibronectins
Gene Expression Regulation
Neoplastic
030104 developmental biology
Endocrinology
Receptors
Estrogen
Oncology
030220 oncology & carcinogenesis
Cancer research
Molecular Medicine
Female
Signal transduction
Proto-Oncogene Proteins c-akt
GPER
Signal Transduction
Zdroj: Molecular Oncology. 10:775-788
ISSN: 1574-7891
Popis: 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.
Databáze: OpenAIRE
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