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

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

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 sile...

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Main Authors: Eunkyung Lee, Ahyoung Choi, Yukyung Jun, Namhee Kim, Jong In Yook, Soo Youl Kim, Sanghyuk Lee, Sang Won Kang
Format: Article
Language:English
Published: Elsevier 2020-01-01
Series:Redox Biology
Online Access:http://www.sciencedirect.com/science/article/pii/S2213231719310481
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spelling doaj-56bc364caa3c49b685bf7870b8e11b902020-11-25T01:36:57ZengElsevierRedox Biology2213-23172020-01-0129Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signalingEunkyung Lee0Ahyoung Choi1Yukyung Jun2Namhee Kim3Jong In Yook4Soo Youl Kim5Sanghyuk Lee6Sang Won Kang7Department of Life Science and Ewha Womans University, Seoul, 03760, South KoreaDepartment of Life Science and Ewha Womans University, Seoul, 03760, South Korea; Bio-Information Science, Ewha Womans University, Seoul, 03760, South KoreaDepartment of Life Science and Ewha Womans University, Seoul, 03760, South Korea; Bio-Information Science, Ewha Womans University, Seoul, 03760, South KoreaDepartment of Oral Pathology, School of Dentistry, Yonsei University, Seoul, 03722, South KoreaDepartment of Oral Pathology, School of Dentistry, Yonsei University, Seoul, 03722, South KoreaDivision of Basic Science, Research Institute, National Cancer Institute, Goyang, 10408, South KoreaDepartment 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.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 kinasehttp://www.sciencedirect.com/science/article/pii/S2213231719310481
collection DOAJ
language English
format Article
sources DOAJ
author Eunkyung Lee
Ahyoung Choi
Yukyung Jun
Namhee Kim
Jong In Yook
Soo Youl Kim
Sanghyuk Lee
Sang Won Kang
spellingShingle Eunkyung Lee
Ahyoung Choi
Yukyung Jun
Namhee Kim
Jong In Yook
Soo Youl Kim
Sanghyuk Lee
Sang Won Kang
Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling
Redox Biology
author_facet Eunkyung Lee
Ahyoung Choi
Yukyung Jun
Namhee Kim
Jong In Yook
Soo Youl Kim
Sanghyuk Lee
Sang Won Kang
author_sort Eunkyung Lee
title Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling
title_short Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling
title_full Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling
title_fullStr Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling
title_full_unstemmed Glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via FAK signaling
title_sort glutathione peroxidase-1 regulates adhesion and metastasis of triple-negative breast cancer cells via fak signaling
publisher Elsevier
series Redox Biology
issn 2213-2317
publishDate 2020-01-01
description 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
url http://www.sciencedirect.com/science/article/pii/S2213231719310481
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