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 resumed in the TNBC cell lines. Such restored 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, the substrate of Gpx1, H2O2, directly inhibits the FAK kinase activity. As a result, depletion of Gpx1 greatly suppresses lung metastasis of TNBC cells in vivo. Overall, our study identifies that Gpx1 is a redox safeguard of FAK kinase and allows for a therapeutic process to effectively control the metastasis of deadly malignant TNBC.Support or Funding InformationNational Research Foundation of Korea (2018R1A2B3006323 and 2017M3A9B6073098)National R&D Program for Cancer Control (1420280).
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