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Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling

  • 주제(키워드) Glutathione peroxidase , Triple-negative breast cancer , Metastasis , Adhesion , Focal adhesion kinase
  • 주제(기타) Biochemistry & Molecular Biology
  • 설명문(일반) [Lee, Eunkyung; Choi, Ahyoung; Jun, Yukyung; Lee, Sanghyuk; Kang, Sang Won] Dept Life Sci, Seoul 03760, South Korea; [Lee, Eunkyung; Choi, Ahyoung; Jun, Yukyung; Lee, Sanghyuk; Kang, Sang Won] Ewha Womans Univ, Seoul 03760, South Korea; [Choi, Ahyoung; Jun, Yukyung; Lee, Sanghyuk] Ewha Womans Univ, Bioinformat Sci, Seoul 03760, South Korea; [Kim, Namhee; Yook, Jong In] Yonsei Univ, Sch Dent, Dept Oral Pathol, Seoul 03722, South Korea; [Kim, Soo Youl] Natl Canc Inst, Res Inst, Div Basic Sci, Goyang 10408, South Korea
  • 등재 SCIE, SCOPUS
  • OA유형 Green Published, gold
  • 발행기관 ELSEVIER
  • 발행년도 2020
  • 총서유형 Journal
  • URI http://www.dcollection.net/handler/ewha/000000165966
  • 본문언어 영어
  • Published As http://dx.doi.org/10.1016/j.redox.2019.101391
  • PubMed https://pubmed.ncbi.nlm.nih.gov/31926619

초록/요약

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 Gpxl 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.

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