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

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 o...

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Bibliographic Details
Published in:Scientific reports 2021-01, Vol.11 (1), p.1247-1247, Article 1247
Main Authors: Ko, Eunsun, Kim, Dasom, Min, Dong Wha, Kwon, Seung-Hae, Lee, Ji-Yun
Format: Article
Language:English
Subjects:
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Angiogenesis
Antioxidants
Cell adhesion & migration
Cell migration
Cell morphology
Cytology
Cytoplasm
Enzymes
Humanities and Social Sciences
Inflammation
Lung cancer
Motility
multidisciplinary
Non-small cell lung carcinoma
Oxidative stress
RhoA protein
Science
Science (multidisciplinary)
Signal transduction
Small cell lung carcinoma
Transcription
Tumors
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-81021-0