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Erschienen in: Breast Cancer Research and Treatment 1/2019

19.11.2018 | Preclinical study

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

verfasst von: Jingjing Liu, Lei Liu, Ernesto Yagüe, Qianxi Yang, Teng Pan, Hui Zhao, Yunhui Hu, Jin Zhang

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 1/2019

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

Our data demonstrate that GGNBP2 suppresses cancer aggressiveness by inhibition of IL-6/STAT3 activation in TNBC.
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Metadaten
Titel
GGNBP2 suppresses triple-negative breast cancer aggressiveness through inhibition of IL-6/STAT3 signaling activation
verfasst von
Jingjing Liu
Lei Liu
Ernesto Yagüe
Qianxi Yang
Teng Pan
Hui Zhao
Yunhui Hu
Jin Zhang
Publikationsdatum
19.11.2018
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 1/2019
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-5052-z

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