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

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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 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
Volume29
DOIs
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

Fingerprint

Dive into the research topics of 'Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling'. Together they form a unique fingerprint.

Cite this