Breast Cancer Research and Treatment

, Volume 174, Issue 1, pp 65–78 | Cite as

GGNBP2 suppresses triple-negative breast cancer aggressiveness through inhibition of IL-6/STAT3 signaling activation

  • Jingjing Liu
  • Lei Liu
  • Ernesto Yagüe
  • Qianxi Yang
  • Teng Pan
  • Hui Zhao
  • Yunhui HuEmail author
  • Jin ZhangEmail author
Preclinical study



Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, lacking effective targeted therapies, and whose underlying mechanisms are still unclear. The gene coding for Gametogenetin-binding protein (GGNBP2), also known as Zinc Finger Protein 403 (ZNF403), is located on chromosome 17q12-q23, a region known as a breast cancer susceptibility locus. We have previously reported that GGNBP2 functions as a tumor suppressor in estrogen receptor-positive breast cancer. The aim of this study was to evaluate the role and mechanisms of GGNBP2 in TNBC.


The effect of GGNBP2 on TNBC aggressiveness was investigated both in vitro and in vivo. The protein and mRNA expression levels were analyzed by western blotting and reverse transcription quantitative polymerase chain reaction, respectively. Fluorescence-activated cell sorting analysis was used to evaluate the cell cycle distribution and cell apoptosis. Immunohistochemistry was used to determine the expression of GGNBP2 in breast cancer tissues.


We find that GGNBP2 expression decreases in TNBC tissues and is associated with the outcome of breast cancer patients. Furthermore, experimental overexpression of GGNBP2 in MDA-MB-231 and Cal51 cells suppresses cell proliferation, migration and invasion, reduces the cancer stem cell subpopulation, and promotes cell apoptosis in vitro as well as inhibits tumor growth in vivo. In these cell models, overexpression of GGNBP2 decreases the activation of IL-6/STAT3 signaling.


Our data demonstrate that GGNBP2 suppresses cancer aggressiveness by inhibition of IL-6/STAT3 activation in TNBC.


Triple-negative breast cancer STAT3 GGNBP2 



This study was supported by the Tianjin Natural Sciences Foundation (17JCQNJC09900 to YH) and the National Natural Science Foundation of China (No. 81672623 to ZJ). EY thanks Breast Cancer Now for supporting research in his laboratory.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

10549_2018_5052_MOESM1_ESM.docx (1.7 mb)
Supplementary material 1 (DOCX 1.8 mb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.The 3rd Department of Breast Cancer, Treatment and Research Center, China Tianjin Breast Cancer Prevention, Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center of CancerTianjinPeople’s Republic of China
  2. 2.Division of Cancer, Faculty of Medicine, Cancer Research CenterImperial College LondonLondonUK

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