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
Affiliations
Eunkyung Lee
Department of Life Science and Ewha Womans University, Seoul, 03760, South Korea
Ahyoung Choi
Department of Life Science and Ewha Womans University, Seoul, 03760, South Korea; Bio-Information Science, Ewha Womans University, Seoul, 03760, South Korea
Yukyung Jun
Department of Life Science and Ewha Womans University, Seoul, 03760, South Korea; Bio-Information Science, Ewha Womans University, Seoul, 03760, South Korea
Namhee Kim
Department of Oral Pathology, School of Dentistry, Yonsei University, Seoul, 03722, South Korea
Jong In Yook
Department of Oral Pathology, School of Dentistry, Yonsei University, Seoul, 03722, South Korea
Soo Youl Kim
Division of Basic Science, Research Institute, National Cancer Institute, Goyang, 10408, South Korea
Sanghyuk Lee
Department of Life Science and Ewha Womans University, Seoul, 03760, South Korea; Bio-Information Science, Ewha Womans University, Seoul, 03760, South Korea; Corresponding author. Department of Life Science and Ewha Womans University, Seoul, 03760, South Korea.
Sang Won Kang
Department of Life Science and Ewha Womans University, Seoul, 03760, South Korea; Corresponding author.
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. Keywords: Glutathione peroxidase, Triple-negative breast cancer, Metastasis, Adhesion, Focal adhesion kinase
