Quercetin restrains TGF-β1-induced epithelial–mesenchymal transition by inhibiting Twist1 and regulating E-cadherin expression

Feng, Jing; Song, Dalong; Jiang, Siyuan; Yang, Xiaohui; Ding, Tingting; Zhang, Hong; Luo, Jie; Liao, Jun; Yin, Qian

doi:10.1016/j.bbrc.2018.02.044

Cited by 55 publications

(38 citation statements)

References 20 publications

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“…The lack of beta-catenin and E-cadherin membrane localization resulted in a loss of attachment to the actin cytoskeleton, and the disassembly of these adherens junctions components led to a loss of epithelial integrity and polarity [62]. In further support of our findings, studies on human cancer cell lines have shown that quercetin increases the membranous localization of beta-catenin and E-cadherin, leading to improved cell adhesion and reduced metastasis [31,63,64]. These studies suggest that in our quercetin treated dysplastic kidneys, the re-establishment of beta-catenin and E-cadherin expression in membrane of the transitioning mesenchyme may also lead to a re-attachment to the actin cytoskeleton, therefore improving adherens junctions integrity and promoting epithelial transition [62].…”

Section: Plos Onesupporting

confidence: 78%

Quercetin treatment reduces the severity of renal dysplasia in a beta-catenin dependent manner

et al. 2020

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Renal dysplasia, the major cause of childhood renal failure, is characterized by defective branching morphogenesis and nephrogenesis. Beta-catenin, a transcription factor and cell adhesion molecule, is markedly increased in the nucleus of kidney cells in human renal dysplasia and contributes to its pathogenesis by altering target genes that are essential for kidney development. Quercetin, a naturally occurring flavonoid, reduces nuclear beta-catenin levels and reduces beta-catenin transcriptional activity. In this study, we utilized wild type and dysplastic mouse kidney organ explants to determine if quercetin reduces beta-catenin activity during kidney development and whether it improves the severity of renal dysplasia. In wild type kidney explants, quercetin treatment resulted in abnormal branching morphogenesis and nephrogenesis in a dose dependent manner. In wild type embryonic kidneys, quercetin reduced nuclear beta-catenin expression and decreased expression of beta-catenin target genes Pax2, Six2, and Gdnf, which are essential for kidney development. Our RD B mouse model of renal dysplasia recapitulates the overexpression of beta-catenin and histopathological changes observed in human renal dysplasia. RD B kidneys treated with quercetin resulted in improvements in the overall histopathology, tissue organization, ureteric branching morphogenesis, and nephrogenesis. Quercetin treatment also resulted in reduced nuclear beta-catenin and reduced Pax2 expression. These improvements were associated with the proper organization of vimentin, NCAM, and E-cadherin, and a 45% increase in the number of developing and maturing nephrons. Further, our results show that in human renal dysplasia, beta-catenin, vimentin, and e-cadherin also have abnormal expression patterns. Taken together, these data demonstrate that quercetin treatment reduces nuclear beta-catenin and this is associated with improved epithelial organization of developing nephrons, resulting in increased developing nephrons and a partial rescue of renal dysplasia.

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Section: Plos Onesupporting

confidence: 78%

Quercetin treatment reduces the severity of renal dysplasia in a beta-catenin dependent manner

et al. 2020

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“…It has been found that transforming growth factor-beta 1 (TGF-β1) induces epithelial mesenchymal transition (EMT) in various cancer cells, promoting motility and invasiveness [46,47]. Additionally, TGF-β1 treatment reduces the enhanced expression of Snail1 and Twist1 and, subsequently, the expression of E-cadherin [47].…”

Section: Discussionmentioning

confidence: 99%

Quercetin Inhibits Cell Survival and Metastatic Ability via the EMT-Mediated Pathway in Oral Squamous Cell Carcinoma

et al. 2020

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This study aimed to investigate whether quercetin exerts anticancer effects on oral squamous cell carcinoma (OSCC) cell lines and to elucidate its mechanism of action. These anticancer effects in OSCC cells were assessed using an MTT assay, flow cytometry (to assess the cell cycle), wound-healing assay, invasion assay, Western blot analysis, gelatin zymography, and immunofluorescence. To investigate whether quercetin also inhibits transforming growth factor β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) in human keratinocyte cells, HaCaT cells were treated with TGF-β1. Overall, our results strongly suggest that quercetin suppressed the viability of OSCC cells by inducing cell cycle arrest at the G2/M phase. However, quercetin did not affect cell viability of human keratinocytes such as HaCaT (immortal keratinocyte) and nHOK (primary normal human oral keratinocyte) cells. Additionally, quercetin suppresses cell migration through EMT and matrix metalloproteinase (MMP) in OSCC cells and decreases TGF-β1-induced EMT in HaCaT cells. In conclusion, this study is the first, to our knowledge, to demonstrate that quercetin can inhibit the survival and metastatic ability of OSCC cells via the EMT-mediated pathway, specifically Slug. Quercetin may thus provide a novel pharmacological approach for the treatment of OSCCs.Molecules 2020, 25, 757 2 of 15 Statistical AnalysesStatistical analyses were performed by a one-way analysis of variance (ANOVA) followed by a Bonferroni post-test, whereby three or more experimental groups were compared. p-values of < 0.05 were considered statistically significant. All data are the means ± standard error of the mean (SEM).

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“…37 Quercetin downregulated Twist1 and simultaneously increased the level of E-cadherin. Quercetin inhibited TGFβ1-mediated EMT in SW480 cells.…”

Section: Regulation Of Tgf/smad and Shh/gli Signaling By Quercetin:mentioning

confidence: 99%

“…Quercetin inhibited TGFβ1-mediated EMT in SW480 cells. 37 Quercetin downregulated Twist1 and simultaneously increased the level of E-cadherin. Twist1 expression was found to be dramatically enhanced in TGFβ1-treated SW480 cells but was clearly reduced in cells treated with quercetin and TGFβ1.…”

Section: And Shh/gli Signaling By Quercetin: Missing Pieces Of An Incmentioning

confidence: 99%

“…Twist1 expression was found to be dramatically enhanced in TGFβ1-treated SW480 cells but was clearly reduced in cells treated with quercetin and TGFβ1. 37 It seems astonishing to note that quercetin-mediated effects have been extensively studied, but we still have incomplete knowledge related to the regulation of signal transducers of TGF pathway. Sma-mothers against decapentaplegic (SMAD) proteins are central players in carcinogenesis.…”

Section: And Shh/gli Signaling By Quercetin: Missing Pieces Of An Incmentioning

confidence: 99%

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Quercetin‐mediated regulation of signal transduction cascades and microRNAs: Natural weapon against cancer

Farooqı

Jabeen

Attar

et al. 2018

J of Cellular Biochemistry

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Recent technological and analytical breakthroughs in genomics and proteomics have deepened our understanding related to the multifaceted nature of cancer. Because of therapeutically challenging nature of cancer, there has been a renewed interest in phytochemistry, and much attention is currently being given to the identification of signaling pathway inhibitors. Data obtained through high-throughput technologies has provided a broader landscape of wiring maps of complex oncogenic signaling networks, thus revealing novel therapeutic opportunities. Increasingly, it is being realized that although our knowledge related to physiological and pathophysiological roles of signal transduction cascades has evolved rapidly, the clinical development of signaling pathway inhibitors has been challenging. Quercetin has attracted considerable attention because of its amazingly high pharmacological value. Research over decades has sequentially shown that quercetin effectively inhibited cancer development and progression. In this review, we have attempted to set the spotlight on the regulation of different cell signaling pathways by quercetin. We partition this multicomponent review into how quercetin effectively regulates the Wnt/β-catenin pathway, Janus kinase-signal transducer and activator of transcription pathway, and vascular endothelial growth factor/vascular endothelial growth factor receptor signaling cascade in different types of cancers. We also provide an overview of the regulation of NOTCH and SHH pathways by quercetin. MicroRNAs (miRNAs) have also emerged as versatile regulators of cancer, and contemporary studies have shed light on the ability of quercetin to control different miRNAs in various cancers. We have scattered information related to NOTCH and SHH pathways, and future studies must converge on the investigation of these pathways to see how quercetin modulates the signaling machinery of these pathways.

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Quercetin restrains TGF-β1-induced epithelial–mesenchymal transition by inhibiting Twist1 and regulating E-cadherin expression

Cited by 55 publications

References 20 publications

Quercetin treatment reduces the severity of renal dysplasia in a beta-catenin dependent manner

Quercetin treatment reduces the severity of renal dysplasia in a beta-catenin dependent manner

Quercetin Inhibits Cell Survival and Metastatic Ability via the EMT-Mediated Pathway in Oral Squamous Cell Carcinoma

Quercetin‐mediated regulation of signal transduction cascades and microRNAs: Natural weapon against cancer

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