Particulate Matter (PM<sub>10</sub>) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung Cells
Air pollution presents a major environmental problem, inducing harmful effects on human health. Particulate matter of 10 μm or less in diameter (PM<sub>10</sub>) is considered an important risk factor in lung carcinogenesis. Epithelial–mesenchymal transition (EMT) is a regulatory program...
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MDPI AG
2021-11-01
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Online Access: | https://www.mdpi.com/1422-0067/22/23/12632 |
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author | Claudia M. García-Cuellar Miguel Santibáñez-Andrade Yolanda I. Chirino Raúl Quintana-Belmares Rocío Morales-Bárcenas Ericka Marel Quezada-Maldonado Yesennia Sánchez-Pérez |
author_facet | Claudia M. García-Cuellar Miguel Santibáñez-Andrade Yolanda I. Chirino Raúl Quintana-Belmares Rocío Morales-Bárcenas Ericka Marel Quezada-Maldonado Yesennia Sánchez-Pérez |
author_sort | Claudia M. García-Cuellar |
collection | DOAJ |
description | Air pollution presents a major environmental problem, inducing harmful effects on human health. Particulate matter of 10 μm or less in diameter (PM<sub>10</sub>) is considered an important risk factor in lung carcinogenesis. Epithelial–mesenchymal transition (EMT) is a regulatory program capable of inducing invasion and metastasis in cancer. In this study, we demonstrated that PM<sub>10</sub> treatment induced phosphorylation of SMAD2/3 and upregulation of SMAD4. We also reported that PM<sub>10</sub> increased the expression and protein levels of <i>TGFB1</i> (TGF-β), as well as EMT markers <i>SNAI1</i> (Snail), <i>SNAI2</i> (Slug), <i>ZEB1</i> (ZEB1), <i>CDH2</i> (N-cadherin), <i>ACTA2</i> (α-SMA), and <i>VIM</i> (vimentin) in the lung A549 cell line. Cell exposed to PM<sub>10</sub> also showed a decrease in the expression of <i>CDH1</i> (E-cadherin). We also demonstrated that expression levels of these EMT markers were reduced when cells are transfected with small interfering RNAs (siRNAs) against <i>TGFB1</i>. Interestingly, phosphorylation of SMAD2/3 and upregulation of SMAD induced by PM<sub>10</sub> were not affected by transfection of <i>TGFB1</i> siRNAs. Finally, cells treated with PM<sub>10</sub> exhibited an increase in the capacity of invasiveness because of EMT induction. Our results provide new evidence regarding the effect of PM<sub>10</sub> in EMT and the acquisition of an invasive phenotype, a hallmark necessary for lung cancer progression. |
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id | doaj.art-41b289432d1546b7bb877ca8bde9d756 |
institution | Directory Open Access Journal |
issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T04:53:08Z |
publishDate | 2021-11-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-41b289432d1546b7bb877ca8bde9d7562023-11-23T02:25:39ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231263210.3390/ijms222312632Particulate Matter (PM<sub>10</sub>) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung CellsClaudia M. García-Cuellar0Miguel Santibáñez-Andrade1Yolanda I. Chirino2Raúl Quintana-Belmares3Rocío Morales-Bárcenas4Ericka Marel Quezada-Maldonado5Yesennia Sánchez-Pérez6Instituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Ciudad de México 14080, MexicoInstituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Ciudad de México 14080, MexicoUnidad de Biomedicina, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Los Reyes Iztacala, Tlalnepantla 54090, Estado de México, MexicoInstituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Ciudad de México 14080, MexicoInstituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Ciudad de México 14080, MexicoInstituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Ciudad de México 14080, MexicoInstituto Nacional de Cancerología (INCan), Subdirección de Investigación Básica, San Fernando No. 22, Ciudad de México 14080, MexicoAir pollution presents a major environmental problem, inducing harmful effects on human health. Particulate matter of 10 μm or less in diameter (PM<sub>10</sub>) is considered an important risk factor in lung carcinogenesis. Epithelial–mesenchymal transition (EMT) is a regulatory program capable of inducing invasion and metastasis in cancer. In this study, we demonstrated that PM<sub>10</sub> treatment induced phosphorylation of SMAD2/3 and upregulation of SMAD4. We also reported that PM<sub>10</sub> increased the expression and protein levels of <i>TGFB1</i> (TGF-β), as well as EMT markers <i>SNAI1</i> (Snail), <i>SNAI2</i> (Slug), <i>ZEB1</i> (ZEB1), <i>CDH2</i> (N-cadherin), <i>ACTA2</i> (α-SMA), and <i>VIM</i> (vimentin) in the lung A549 cell line. Cell exposed to PM<sub>10</sub> also showed a decrease in the expression of <i>CDH1</i> (E-cadherin). We also demonstrated that expression levels of these EMT markers were reduced when cells are transfected with small interfering RNAs (siRNAs) against <i>TGFB1</i>. Interestingly, phosphorylation of SMAD2/3 and upregulation of SMAD induced by PM<sub>10</sub> were not affected by transfection of <i>TGFB1</i> siRNAs. Finally, cells treated with PM<sub>10</sub> exhibited an increase in the capacity of invasiveness because of EMT induction. Our results provide new evidence regarding the effect of PM<sub>10</sub> in EMT and the acquisition of an invasive phenotype, a hallmark necessary for lung cancer progression.https://www.mdpi.com/1422-0067/22/23/12632PM<sub>10</sub><i>TGFB1</i>A549epithelial–mesenchymal transitioninvasioncancer hallmark |
spellingShingle | Claudia M. García-Cuellar Miguel Santibáñez-Andrade Yolanda I. Chirino Raúl Quintana-Belmares Rocío Morales-Bárcenas Ericka Marel Quezada-Maldonado Yesennia Sánchez-Pérez Particulate Matter (PM<sub>10</sub>) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung Cells International Journal of Molecular Sciences PM<sub>10</sub> <i>TGFB1</i> A549 epithelial–mesenchymal transition invasion cancer hallmark |
title | Particulate Matter (PM<sub>10</sub>) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung Cells |
title_full | Particulate Matter (PM<sub>10</sub>) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung Cells |
title_fullStr | Particulate Matter (PM<sub>10</sub>) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung Cells |
title_full_unstemmed | Particulate Matter (PM<sub>10</sub>) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung Cells |
title_short | Particulate Matter (PM<sub>10</sub>) Promotes Cell Invasion through Epithelial–Mesenchymal Transition (EMT) by TGF-β Activation in A549 Lung Cells |
title_sort | particulate matter pm sub 10 sub promotes cell invasion through epithelial mesenchymal transition emt by tgf β activation in a549 lung cells |
topic | PM<sub>10</sub> <i>TGFB1</i> A549 epithelial–mesenchymal transition invasion cancer hallmark |
url | https://www.mdpi.com/1422-0067/22/23/12632 |
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