Nrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells

Abstract Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of several antioxidant and anti-inflammatory enzymes. It binds to its endogenous inhibitor Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm under normal conditions. Various endogenous or enviro...

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Autores principales:	Eunsun Ko, Dasom Kim, Dong Wha Min, Seung-Hae Kwon, Ji-Yun Lee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1e2ce9ed5c914ae19477f26689d4bc0f
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spelling	oai:doaj.org-article:1e2ce9ed5c914ae19477f26689d4bc0f2021-12-02T14:01:33ZNrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells10.1038/s41598-021-81021-02045-2322https://doaj.org/article/1e2ce9ed5c914ae19477f26689d4bc0f2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81021-0https://doaj.org/toc/2045-2322Abstract Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of several antioxidant and anti-inflammatory enzymes. It binds to its endogenous inhibitor Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm under normal conditions. Various endogenous or environmental oxidative stresses can disrupt the Nrf2/Keap1 complex, allowing Nrf2 to translocate into the nucleus, where it induces the transcription of various cytoprotective enzymes by binding to antioxidant responsive elements. These enzymes have been reported to play a role in regulating tumour growth, angiogenesis, and chemoprevention. Invasion and migration are the most harmful aspects of cancer; they directly impacts the patients’ survival. Although the roles of Keap1/Nrf2 and their downstream genes in various cancers have been widely documented, their role in regulating cell motility still remains unclear, particularly in cancer cells. We observed that Nrf2 suppression following treatment with brusatol in non-small-cell lung cancer (NSCLC) cells with either exogenously introduced Keap1 or siNrf2 resulted in the inhibition of cell migration and invasion, with shrinking cell morphology due to decreased focal adhesions via inhibition of the RhoA–ROCK1 pathway. Nrf2 overexpression showed opposite results. Thus, the Nrf2/Keap1 pathway may affect cell motility by dysregulating the RhoA–ROCK1 signalling pathway in NSCLC.Eunsun KoDasom KimDong Wha MinSeung-Hae KwonJi-Yun LeeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eunsun Ko Dasom Kim Dong Wha Min Seung-Hae Kwon Ji-Yun Lee Nrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells
description	Abstract Nuclear factor-erythroid 2-related factor 2 (Nrf2) is a key transcriptional regulator of several antioxidant and anti-inflammatory enzymes. It binds to its endogenous inhibitor Kelch-like ECH-associated protein 1 (Keap1) in the cytoplasm under normal conditions. Various endogenous or environmental oxidative stresses can disrupt the Nrf2/Keap1 complex, allowing Nrf2 to translocate into the nucleus, where it induces the transcription of various cytoprotective enzymes by binding to antioxidant responsive elements. These enzymes have been reported to play a role in regulating tumour growth, angiogenesis, and chemoprevention. Invasion and migration are the most harmful aspects of cancer; they directly impacts the patients’ survival. Although the roles of Keap1/Nrf2 and their downstream genes in various cancers have been widely documented, their role in regulating cell motility still remains unclear, particularly in cancer cells. We observed that Nrf2 suppression following treatment with brusatol in non-small-cell lung cancer (NSCLC) cells with either exogenously introduced Keap1 or siNrf2 resulted in the inhibition of cell migration and invasion, with shrinking cell morphology due to decreased focal adhesions via inhibition of the RhoA–ROCK1 pathway. Nrf2 overexpression showed opposite results. Thus, the Nrf2/Keap1 pathway may affect cell motility by dysregulating the RhoA–ROCK1 signalling pathway in NSCLC.
format	article
author	Eunsun Ko Dasom Kim Dong Wha Min Seung-Hae Kwon Ji-Yun Lee
author_facet	Eunsun Ko Dasom Kim Dong Wha Min Seung-Hae Kwon Ji-Yun Lee
author_sort	Eunsun Ko
title	Nrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells
title_short	Nrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells
title_full	Nrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells
title_fullStr	Nrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells
title_full_unstemmed	Nrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells
title_sort	nrf2 regulates cell motility through rhoa–rock1 signalling in non-small-cell lung cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1e2ce9ed5c914ae19477f26689d4bc0f
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Nrf2 regulates cell motility through RhoA–ROCK1 signalling in non-small-cell lung cancer cells

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