Activation of GPER suppresses migration and angiogenesis of triple negative breast cancer via inhibition of NF-κB/IL-6 signals
Authors: Qiao Su
Yan Zhou
Shuwei Liang
Zhuojia Chen
Weidong Wei
Guanmin Jiang
Jun Du
Qiao Liu
Hongsheng Wang
Journal: Cancer letters (2017)
Discipline: CLINICAL MEDICINE
Keywords: Angiogenesis; G-1; GPER; NF-κB; TNBC.
Affiliations: Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China., Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China., Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China., Laboratory Animal Center, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China., Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: .

Abstract:  Triple-negative breast cancer (TNBC) is characterized by high vascularity and frequent metastasis. Here, we found that activation of G protein-coupled estrogen receptor (GPER) by its specific agonist G-1 can significantly inhibit interleukin 6 (IL-6) and vascular endothelial growth factor A (VEGF-A). TNBC tissue microarrays from 100 TNBC patients revealed GPER is negatively associated with IL-6 levels and higher grade and stage. Activation of GPER or anti-IL-6 antibody can inhibit both in vitro tube formation of human umbilical vein endothelial cells (HUVECs) and migration of TNBC cells. While recombinant IL-6 supplementary can significantly reverse the inhibitory effects of G-1, suggesting the essential role of IL-6 in G-1 induced suppression of angiogenesis and invasiveness of TNBC cells. G-1 treatment decreased the phosphorylation, nuclear localization, transcriptional activities of NF-κB and suppressed its binding with IL-6 promoter. BAY11-7028, the inhibitor of NF-κB, can mimic the effect of G-1 to suppression of IL-6 and VEGF-A. While over expression of p65 can attenuate the inhibitory effects of G-1 on IL-6 and VEGF expression. The suppression of IL-6 by G-1 can further inhibit HIF-1α and STAT3 signals in TNBC cells by inhibition their expression, phosphorylation and/or nuclear localization. Moreover, G-1 also inhibited the in vivo NF-κB/IL-6 signals and angiogenesis and metastasis of MDA-MB-231 xenograft tumors. In conclusion, our study demonstrated that activation of GPER can suppress migration and angiogenesis of TNBC via inhibition of NF-κB/IL-6 signals, therefore it maybe act as an important target for TNBC treatment. 

Retracted: No

PubPeer comments:
 Corrigendum to u201cActivation of GPER suppresses migration and angiogenesis of triple negative breast cancer via inhibition of NF-u03baB IL-6 signalsu201d [Cancer Lett. 386 (2017) 12u201323] https: www.sciencedirect.com science article pii S0304383517306626?via%3Dihub , 
 The GAPDH band in Fig. 5B is cut from that from Fig. 6A. ![file] , 
 Dear Dr Stegnus, Thanks very much for your kind attention and pointing out the problems in our article. We will seriously check and verify the pictures and original data of the article and actively contact with editors of the journal. We will make a reply about this. Thank you for your comments. ,