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

19 Scopus citations

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
StatePublished - Jan 2020

Keywords

  • Adhesion
  • Focal adhesion kinase
  • Glutathione peroxidase
  • Metastasis
  • Triple-negative breast cancer

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