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

Title
Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling
Authors
Lee, EunkyungChoi, AhyoungJun, YukyungKim, NamheeYook, Jong InKim, Soo YoulLee, SanghyukKang, Sang Won
Ewha Authors
이상혁강상원
SCOPUS Author ID
이상혁scopus; 강상원scopus
Issue Date
2020
Journal Title
REDOX BIOLOGY
ISSN
2213-2317JCR Link
Citation
REDOX BIOLOGY vol. 29
Keywords
Glutathione peroxidaseTriple-negative breast cancerMetastasisAdhesionFocal adhesion kinase
Publisher
ELSEVIER
Indexed
SCIE; SCOPUS WOS scopus
Document Type
Article
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 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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DOI
10.1016/j.redox.2019.101391
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자연과학대학 > 생명과학전공 > Journal papers
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