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...

Full description

Bibliographic Details
Main Authors: Claudia M. García-Cuellar, Miguel Santibáñez-Andrade, Yolanda I. Chirino, Raúl Quintana-Belmares, Rocío Morales-Bárcenas, Ericka Marel Quezada-Maldonado, Yesennia Sánchez-Pérez
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/23/12632
_version_ 1797507767429234688
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.
first_indexed 2024-03-10T04:53:08Z
format Article
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
publisher MDPI AG
record_format Article
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
work_keys_str_mv AT claudiamgarciacuellar particulatematterpmsub10subpromotescellinvasionthroughepithelialmesenchymaltransitionemtbytgfbactivationina549lungcells
AT miguelsantibanezandrade particulatematterpmsub10subpromotescellinvasionthroughepithelialmesenchymaltransitionemtbytgfbactivationina549lungcells
AT yolandaichirino particulatematterpmsub10subpromotescellinvasionthroughepithelialmesenchymaltransitionemtbytgfbactivationina549lungcells
AT raulquintanabelmares particulatematterpmsub10subpromotescellinvasionthroughepithelialmesenchymaltransitionemtbytgfbactivationina549lungcells
AT rociomoralesbarcenas particulatematterpmsub10subpromotescellinvasionthroughepithelialmesenchymaltransitionemtbytgfbactivationina549lungcells
AT erickamarelquezadamaldonado particulatematterpmsub10subpromotescellinvasionthroughepithelialmesenchymaltransitionemtbytgfbactivationina549lungcells
AT yesenniasanchezperez particulatematterpmsub10subpromotescellinvasionthroughepithelialmesenchymaltransitionemtbytgfbactivationina549lungcells