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

Eunkyung Lee, Ahyoung Choi, Yukyung Jun, Namhee Kim, Jong In Yook, Soo Youl Kim, Sanghyuk Lee, Sang Won Kang

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21 Citations (Scopus)


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 Gpx1 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.

Original languageEnglish
Article number101391
JournalRedox Biology
Publication statusPublished - 2020 Jan

Bibliographical note

Funding Information:
We thank Prof. Eok-Soo Oh and Dr. Eun-Woo Lee for sharing antibodies and the lab members for technical assistance. This study was supported by grants from the National Research Foundation of Korea ( 2018R1A2B3006323 and 2017M3A9B6073098 ) and the National R&D Program for Cancer Control ( 1420280 ). Appendix A

Publisher Copyright:
© 2019 The Authors

All Science Journal Classification (ASJC) codes

  • Organic Chemistry
  • Clinical Biochemistry


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