LW1497, an Inhibitor of Malate Dehydrogenase, Suppresses TGF-β1-Induced Epithelial-Mesenchymal Transition in Lung Cancer Cells by Downregulating Slug

LW1497 suppresses the expression of the hypoxia-inducing factor (HIF)-1α inhibiting malate dehydrogenase. Although hypoxia and HIF-1α are known to be important in cancer, LW1497 has not been therapeutically applied to cancer yet. Thus, we investigated the effect of LW1497 on the epithelial-mesenchymal transition (EMT) of lung cancer cells. A549 and H1299 lung cancer cells were induced to undergo via TGF-β1 treatment, resulting in the downregulation of E-cadherin and upregulation of N-cadherin and Vimentin concurrently with increases in the migration and invasion capacities of the cells. These effects of TGF-β1 were suppressed upon co-treatment of the cells with LW1497. An RNA-seq analysis revealed that LW1497 induced differential expression of genes related to hypoxia, RNA splicing, angiogenesis, cell migration, and metastasis in the A549 lung cancer cell lines. We confirmed the differential expression of Slug, an EMT-related transcription factor. Results from Western blotting and RT-PCR confirmed that LW1497 inhibited the expression of EMT markers and Slug. After orthotopically transplanting A549 cancer cells into mice, LW1497 was administered to examine whether the lung cancer progression was inhibited. We observed that LW1497 reduced the area of cancer. In addition, the results from immunohistochemical analyses showed that LW1497 downregulated EMT markers and Slug. In conclusion, LW1497 suppresses cancer progression through the inhibition of EMT by downregulating Slug.

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Luteolin attenuates TGF-β1-induced epithelial–mesenchymal transition of lung cancer cells by interfering in the PI3K/Akt–NF-κB–Snail pathway

Life Sciences ◽

10.1016/j.lfs.2013.10.004 ◽

2013 ◽

Vol 93 (24) ◽

pp. 924-933 ◽

Cited By ~ 42

Author(s):

Kun-Chieh Chen ◽

Chiu-Yuan Chen ◽

Chih-Ju Lin ◽

Tsung-Ying Yang ◽

Tzu-Hsiu Chen ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Lung Cancer Cells ◽

Mesenchymal Transition ◽

Tgf Β1

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Corrigendum to “Luteolin attenuates TGF-β1-induced epithelial–mesenchymal transition of lung cancer cells by interfering in the PI3K/Akt–NF-κB–Snail pathway”. [Life Sci 94 (2013) 924–933]

Life Sciences ◽

10.1016/j.lfs.2014.07.001 ◽

2014 ◽

Vol 109 (2) ◽

pp. 127 ◽

Cited By ~ 1

Author(s):

Kun-Chieh Chen ◽

Chiu-Yuan Chen ◽

Chih-Ju Lin ◽

Tsung-Ying Yang ◽

Tzu-Hsiu Chen ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Lung Cancer Cells ◽

Mesenchymal Transition ◽

Tgf Β1

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Snail1-dependent cancer-associated fibroblasts induce epithelial-mesenchymal transition in lung cancer cells via exosomes

QJM ◽

10.1093/qjmed/hcz093 ◽

2019 ◽

Vol 112 (8) ◽

pp. 581-590 ◽

Cited By ~ 16

Author(s):

J You ◽

M Li ◽

L M Cao ◽

Q H Gu ◽

P B Deng ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Conditioned Medium ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Negative Control ◽

Lung Cancer Cells ◽

Cancer Associated Fibroblasts ◽

Mesenchymal Transition ◽

E Cadherin

Abstract Background Epithelial-mesenchymal transition (EMT) is an essential component of metastasis. Our previous study demonstrated that cancer-associated fibroblasts (CAFs) induce EMT in lung cancer cells. In recent years, many studies have demonstrated that CAFs induce metastasis and drug resistance in cancer cells via exosomes. Aim We sought to discover the mechanism underlying how CAFs induce EMT in lung cancer cells, unveiling the role of exosomes in lung cancer progression. Design We cultured lung cancer cell (i) with control medium, normal fibroblasts (NFs) or CAFs; (ii) with SNAI1-transfected or NC (negative control)-transfected CAFs; (iii) with exosomes extracted from NF- or CAF-conditioned medium; (iv) with exosomes released by SNAI1 or NC-transfected CAFs; (v) with CAF-conditioned medium or exosome-depleted CAF-conditioned medium. Methods qRT-PCR was conducted to examine the expression of CDH1 (gene of E-cadherin) and VIM (gene of Vimentin), western blotting was conducted to examine E-cadherin and vimentin levels in lung cancer cells. Results Exosomes released by CAFs-promoted EMT in lung cancer cells. Interestingly, SNAI1 levels in exosomes secreted from CAFs were correlated with SNAI1 expression in CAFs. Furthermore, the level of SNAI1 in exosomes was crucial for inducing EMT in lung cancer cells. Finally, treatment of CAFs with GW4869, an inhibitor of exosome release, noticeably inhibited their EMT-inducing effect on recipient epithelial cells. Conclusions The molecular mechanism underlying how CAFs induce EMT in cancer cells may be that CAFs deliver SNAI1 to recipient cancer cells via exosomes.

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LncRNA LCPAT1 Mediates Smoking/ Particulate Matter 2.5-Induced Cell Autophagy and Epithelial-Mesenchymal Transition in Lung Cancer Cells via RCC2

Cellular Physiology and Biochemistry ◽

10.1159/000490220 ◽

2018 ◽

Vol 47 (3) ◽

pp. 1244-1258 ◽

Cited By ~ 17

Author(s):

Hongyan Lin ◽

Xiaohong Zhang ◽

Nannan Feng ◽

Ruoyang Wang ◽

Weituo Zhang ◽

...

Keyword(s):

Lung Cancer ◽

Cigarette Smoking ◽

Cancer Cells ◽

Cancer Progression ◽

Epithelial Mesenchymal Transition ◽

Lung Cancer Mortality ◽

Lung Cancer Cells ◽

Mesenchymal Transition ◽

Particulate Matter 2.5

Background/Aims: Ecological studies have shown that air pollution and prevalence of cigarette smoking are positively correlated. Evidence also suggests a synergistic effect of cigarette smoking and PM2.5 exposure (Environmental Particulate Matter ≤ 2.5 µm in diameter) on lung cancer risk. We aimed to evaluate the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality and determine its underlying mechanisms in vitro. Methods: “MOVER” method was used to analyze the interaction between smoking prevalence and PM2.5 pollution in relation to lung cancer mortality. Cell autophagy and malignant behaviors induced by cigarette smoke extract (CSE) and PM2.5 exposure were examined in vitro. Gene expression was examined by qRT-PCR and western blot. RNA and protein interaction was determined using a RNA binding protein immunoprecipitation assay. Results: An increased risk for lung cancer death (RERI (the relative excess risk) =0.28) was observed with a synergistic interaction between cigarette smoking and PM2.5 pollution. Cell migration, invasion, EMT (epithelial-mesenchymal transition) and autophagy were elevated when lung cancer cells were treated with CSE and PM2.5 in combination. A lncRNA, named lung cancer progression-association transcript 1 (LCPAT1), was up-regulated after the treatment of CSE and PM2.5, and knocking down the lncRNA impaired the effect of CSE and PM2.5 on lung cancer cells. In addition, LCPAT1 was shown to bind to RCC2, and RCC2 mediated the effect of LCPAT1 on cell autophagy, migration, invasion and EMT in lung cancer. Conclusions: Our results suggest that combined exposure to CSE and PM2.5 induces LCPAT1 expression, which up-regulates autophagy, and promotes lung cancer progression via RCC2.

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TGF-β1-induced epithelial–mesenchymal transition in lung cancer cells involves upregulation of miR-9 and downregulation of its target, E-cadherin

Cellular & Molecular Biology Letters ◽

10.1186/s11658-017-0053-1 ◽

2017 ◽

Vol 22 (1) ◽

Cited By ~ 21

Author(s):

Hui Wang ◽

Qian Wu ◽

Ying Zhang ◽

Hua-Nan Zhang ◽

Yong-Bin Wang ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Epithelial Mesenchymal Transition ◽

Lung Cancer Cells ◽

Mesenchymal Transition ◽

Tgf Β1 ◽

E Cadherin

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The Effect of Suppression Taurine on Relocation and Epithelial-Mesenchymal Transition in Mankind Lung Cancer Cells

Journal of Healthcare Engineering ◽

10.1155/2021/6656080 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Yongyan Deng ◽

Hongjin Li ◽

Yujiao Tang

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Zinc Finger ◽

Zinc Finger Protein ◽

Epithelial Mesenchymal Transition ◽

Antioxidant Properties ◽

Lung Cancer Cells ◽

Mesenchymal Transition ◽

Taurine Treatment ◽

Emt Markers

Aim. Taurine is believed to have antioxidant properties and has been implicated in the treatment of neurodegenerative disease, atherosclerosis, coronary heart disease, and prostate cancer. This research focused on taurine inhibition effects of expression related to migration and epithelial-mesenchymal transition- (EMT-) A549 study on related genes of human being non-small-cell lung cancer. Methods. MTT assays assessed cell viability and a RadiusTM assay showed that taurine also inhibited the lung cancer cell migration. Using RT-PCR and Western blot, the migration and EMT markers were identified and evaluated. Results. We found that taurine significantly decreased the expression of migration markers matrix metallopeptidase 9 (MMP-9) and vascular endothelial growth factor (VEGF). In contrast, TIMP metallopeptidase inhibitor 1 (TIMP-1) and TIMP metallopeptidase inhibitor 2 (TIMP-2) expressions were increased with taurine treatment. In addition, we found an association between taurine treatment and the expression of EMT markers. The expression of epithelial marker E-cadherin and the mesenchymal marker N-cadherin TWIST-1 was decreased, but the expression of zinc finger protein SNAIL-1 and E-zinc finger homeobox 1 (ZEB-1) was increased. Conclusion. Taken together, our study strongly suggests the therapeutic significance of taurine, which possesses antimigration activity and induces EMT markers expression in lung cancer cells.

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