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Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling

Authors
 Eunkyung Lee  ;  Ahyoung Choi  ;  Yukyung Jun  ;  Namhee Kim  ;  Jong In Yook  ;  Soo Youl Kim  ;  Sanghyuk Lee  ;  Sang Won Kang 
Citation
 REDOX BIOLOGY, Vol.29 : 101391, 2020-01 
Journal Title
REDOX BIOLOGY
Issue Date
2020-01
MeSH
Cell Line, Tumor ; Cell Movement ; Focal Adhesion Kinase 1 ; Glutathione Peroxidase* / genetics ; Humans ; Hydrogen Peroxide ; Signal Transduction ; Triple Negative Breast Neoplasms* / genetics
Keywords
Glutathione peroxidase ; Triple-negative breast cancer ; Metastasis ; Adhesion ; Focal adhesion kinase
Abstract
Triple-negative breast cancer (TNBC) cells, which do not express genes for estrogen receptor (ER), progesterone receptor (PR), and Her2/neu, develop highly aggressive and metastatic tumors resistant to chemo- and hormonal therapies. We found that expression of glutathione peroxidase-1 (Gpx1) is silenced in the non-TNBC cells but significantly maintained in the TNBC cell lines. Such Gpx1 expression plays a vital role in the metastasis of TNBC cells by regulating cell adhesion. Transcriptomic and signaling pathway analyses demonstrate that depletion of Gpxl essentially impairs cell adhesion/spreading by down-regulating FAK/c-Src activation. Mechanistically, Gpx1 interacts with FAK kinase and prevents the kinase inactivation by H2O2, not lipid hydroperoxide. As a result, depletion of Gpx1 suppresses lung metastasis of TNBC cells in vivo. Overall, our study identifies that Gpx1 is a redox safeguard of FAK kinase and its inhibition may provide an effective way to control the metastasis of deadly malignant TNBC.
Files in This Item:
T9992020497.pdf Download
DOI
10.1016/j.redox.2019.101391
Appears in Collections:
2. College of Dentistry (치과대학) > Research Institute (부설연구소) > 1. Journal Papers
2. College of Dentistry (치과대학) > Dept. of Oral Pathology (구강병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Nam Hee(김남희) ORCID logo https://orcid.org/0000-0002-3087-5276
Yook, Jong In(육종인) ORCID logo https://orcid.org/0000-0002-7318-6112
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190272
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