ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling

Yazaki, Kai; Matsuno, Yosuke; Yoshida, Kazufumi; Sherpa, Mingma T.; Nakajima, Masayuki; Matsuyama, Masashi; Kiwamoto, Takumi; Morishima, Yuko; Ishii, Yukio; Hizawa, Nobuyuki

doi:10.1016/j.ejcb.2021.151181

Cited by 36 publications

(33 citation statements)

References 48 publications

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“…Yazaki et al reported that the ROS mediated TGF-β1-induced EMT in A549 cells [ 15 ]. To investigate whether TGF-β1 stimulated ROS generation in A549 and NCI - H460 cells, this study used ROS detection assay kits to detect intracellular ROS levels.…”

Section: Resultsmentioning

confidence: 99%

α-Viniferin and ε-Viniferin Inhibited TGF-β1-Induced Epithelial-Mesenchymal Transition, Migration and Invasion in Lung Cancer Cells through Downregulation of Vimentin Expression

et al. 2022

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Resveratrol has well-known anticancer properties; however, its oligomers, including α-viniferin, ε-viniferin, and kobophenol A, have not yet been well investigated. This is the first study examining the anti-epithelial-mesenchymal transition (EMT) effects of α-viniferin and ε-viniferin on A549, NCI-H460, NCI-H520, MCF-7, HOS, and U2OS cells. The results showed that α-viniferin and ε-viniferin significantly inhibited EMT, invasion and migration in TGF-β1- or IL-1β-induced non-small cell lung cancer. α-Viniferin and ε-viniferin also reversed TGF-β1-induced reactive oxygen species (ROS), MMP2, vimentin, Zeb1, Snail, p-SMAD2, p-SMAD3, and ABCG2 expression in A549 cells. Furthermore, ε-viniferin was found to significantly inhibit lung metastasis in A549 cell xenograft metastatic mouse models. In view of these findings, α-viniferin and ε-viniferin may play an important role in the prevention of EMT and cancer metastasis in lung cancer.

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Section: Resultsmentioning

confidence: 99%

α-Viniferin and ε-Viniferin Inhibited TGF-β1-Induced Epithelial-Mesenchymal Transition, Migration and Invasion in Lung Cancer Cells through Downregulation of Vimentin Expression

et al. 2022

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“…Several mechanisms have been identified in X-ROS/cytokine/ECM signaling-coupled Notch signaling. The first is to act through the coupling of TGFβ1 and NOX4-derived ROS in epithelial cells, where niche factor TGFβ1 induces NOX4 expression (through p38 kinase ( Ning et al, 2002 )), ROS-dependent Nrf2 activation and expression, NOX4-derived ROS production, and Nrf2-dependent Notch signaling ( Yazaki et al, 2021 ), which in turn induces EMT ( Matsuno et al, 2012 ). Herein, Nrf2 stands for nuclear factor erythroid-derived 2-related factor 2, a leucine-zipper transcription factor ( Moi et al, 1994 ).…”

Section: Main Textmentioning

confidence: 99%

“…The production of ROS is primarily controlled by cell metabolism, O 2 , ROS themselves, and several signaling events of niche factors. Examples of these signaling events include the signaling for transforming growth factor-β (TGF-β) ( Hiraga et al, 2013 ; Yan et al, 2014 ; Watson et al, 2016 ; Yazaki et al, 2021 ), epidermal growth factor (EGF) ( Azimi et al, 2017 ; Dustin et al, 2020 ), insulin ( Besse-Patin and Estall, 2014 ), insulin-like growth factor-1 (IGF-1) ( Kang et al, 2016 ), inflammatory and immune-regulatory cytokines such as angiotensin II and tumor necrosis factor-alpha (TNF-α) ( Anilkumar et al, 2008 ), calcium ( Gorlach et al, 2015 ; Feno et al, 2019 ), mechanotransduction ( Sauer et al, 2008 ; Brandes et al, 2014a ), integrin-ECM interactions ( de Rezende et al, 2012 ; Eble and de Rezende, 2014 ), and cell–cell adhesions ( Lim et al, 2008 ). Conversely, ROS modulate the activities of several cell fate-decision factors.…”

Section: Introductionmentioning

confidence: 99%

“…These factors include the oxygen sensor hypoxia-inducible factor (HIF) ( Gerald et al, 2004 ; Saito et al, 2015 ; Kobayashi et al, 2021 ), the mechano-transducer Yes-associated protein (YAP) ( Cho et al, 2020 ), the transducer for the cell differentiation transcription factor Notch, Notch intracellular domain (NICD) ( Cai W.-X. et al, 2014 ; Caliceti et al, 2014 ; Yan et al, 2014 ; Sprouse et al, 2019 ; Yazaki et al, 2021 ), and the immune suppressor programmed death ligand-1 (PD-L1) ( Bailly, 2020 ). Herein, HIF, YAP, and NICD act as a triad in stem cell physiology and tumorigenesis, as they can physically associate to influence each other ( Qiang et al, 2012 ; Hu et al, 2014 ; Manderfield et al, 2015 ; Totaro et al, 2018a ; Zhang X. et al, 2018 ; Engel-Pizcueta and Pujades, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis

Guo

2022

Front. Cell Dev. Biol.

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Organ development, homeostasis, and repair often rely on bidirectional, self-organized cell-niche interactions, through which cells select cell fate, such as stem cell self-renewal and differentiation. The niche contains multiplexed chemical and mechanical factors. How cells interpret niche structural information such as the 3D topology of organs and integrate with multiplexed mechano-chemical signals is an open and active research field. Among all the niche factors, reactive oxygen species (ROS) have recently gained growing interest. Once considered harmful, ROS are now recognized as an important niche factor in the regulation of tissue mechanics and topology through, for example, the HIF-YAP-Notch signaling pathways. These pathways are not only involved in the regulation of stem cell physiology but also associated with inflammation, neurological disorder, aging, tumorigenesis, and the regulation of the immune checkpoint molecule PD-L1. Positive feedback circuits have been identified in the interplay of ROS and HIF-YAP-Notch signaling, leading to the possibility that under aberrant conditions, self-organized, ROS-dependent physiological regulations can be switched to self-perpetuating dysregulation, making ROS a double-edged sword at the interface of stem cell physiology and tumorigenesis. In this review, we discuss the recent findings on how ROS and tissue mechanics affect YAP-HIF-Notch-PD-L1 signaling, hoping that the knowledge can be used to design strategies for stem cell-based and ROS-targeting therapy and tissue engineering.

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“…IR itself, as well as other factors, can activate the Notch pathway ( Kang et al, 2013 ; Grassi et al, 2020 ; Fang et al, 2021 ). The activated Notch pathway can increase cell proliferation by inducing cell EMT and upregulating factors related to cell survival and antiapoptotic processes ( Zhang et al, 2021b ; Pu et al, 2021 ; Yazaki et al, 2021 ), eventually leading to increased resistance to antitumor treatment strategies ( Zhang et al, 2021b ; Pu et al, 2021 ; Yazaki et al, 2021 ). At present, there is no clear clinical cohort study on the relationship between the Notch pathway and RFA, but in addition to radiotherapy and chemotherapy, EMT and other mechanisms have also been found to be closely related to poor prognosis, incomplete ablation, and recurrence of interventional therapies such as RFA and TACE ( Zhang et al, 2017 ; Kuo et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells

et al. 2022

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Radiofrequency ablation (RFA) is a relatively new and effective therapeutic strategy for treating lung squamous cell carcinomas (LSCCs). However, RFA is rarely used in the clinic for LSCC which still suffers from a lack of effective comprehensive treatment strategies. In the present work, we investigate iDNMT, a novel small molecular inhibitor of DNMT1 with a unique structure. In clinical LSCC specimens, endogenous DNMT1 was positively associated with methylation rates of miR-27-3p′s promoter. Moreover, endogenous DNMT1 was negatively correlated with miR-27-3p expression which targets PSEN-1, the catalytic subunit of γ-secretase, which mediates the cleavage and activation of the Notch pathway. We found that DNMT1 increased activation of the Notch pathway in clinical LSCC samples while downregulating miR-27-3p expression and hypermethylation of miR-27-3p′s promoter. In addition of inhibiting activation of the Notch pathway by repressing methylation of the miR-27-3p promoter, treatment of LSCC cells with iDNMT1 also enhanced the sensitivity of LSCC tumor tissues to RFA treatment. These data suggest that iDNMT-induced inhibition of DNMT-1 enhances miR-27-3p expression in LSCC to inhibit activation of the Notch pathway. Furthermore, the combination of iDNMT and RFA may be a promising therapeutic strategy for LSCC.

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ROS-Nrf2 pathway mediates the development of TGF-β1-induced epithelial-mesenchymal transition through the activation of Notch signaling

Cited by 36 publications

References 48 publications

α-Viniferin and ε-Viniferin Inhibited TGF-β1-Induced Epithelial-Mesenchymal Transition, Migration and Invasion in Lung Cancer Cells through Downregulation of Vimentin Expression

α-Viniferin and ε-Viniferin Inhibited TGF-β1-Induced Epithelial-Mesenchymal Transition, Migration and Invasion in Lung Cancer Cells through Downregulation of Vimentin Expression

Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis

A Novel Small Molecular Inhibitor of DNMT1 Enhances the Antitumor Effect of Radiofrequency Ablation in Lung Squamous Cell Carcinoma Cells

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