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.

三阴性乳腺癌 (TNBC) 细胞不表达雌激素受体 (ER)、孕激素受体 (PR) 和 Her2/neu 基因，会发展出对化疗和激素疗法具有抗性的高度侵袭性和转移性肿瘤。我们发现谷胱甘肽过氧化物酶-1 (Gpx1) 的表达在非 TNBC 细胞中被沉默，但在 TNBC 细胞系中显着维持。这种 Gpx1 表达通过调节细胞粘附在 TNBC 细胞的转移中起着至关重要的作用。转录组学和信号通路分析表明，Gpx1 的耗竭通过下调 FAK/c-Src 激活实质上损害了细胞粘附/扩散。从机制上讲，Gpx1 与 FAK 激酶相互作用并防止 H ₂ O _{2使激酶失活}, 不是脂质氢过氧化物。因此，Gpx1 的耗竭抑制了体内 TNBC 细胞的肺转移。总的来说，我们的研究确定 Gpx1 是 FAK 激酶的氧化还原保护剂，其抑制可能提供一种有效的方法来控制致命恶性 TNBC 的转移。