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LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway

BACKGROUND: LIM and SH3 domain protein 1 (LASP1), highly expressed in a variety of tumors, is considered as a novel tumor metastasis biomarker. However, it is unknown which signaling pathway works and how the signal transduces into cell nucleus to drive tumor progression by LASP1. The aim of this st...

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Autores principales: Xue, Qingming, Jiang, Hong, Wang, Jinjie, Wei, Dongshan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668282/
https://www.ncbi.nlm.nih.gov/pubmed/34912481
http://dx.doi.org/10.1155/2021/5277409
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author Xue, Qingming
Jiang, Hong
Wang, Jinjie
Wei, Dongshan
author_facet Xue, Qingming
Jiang, Hong
Wang, Jinjie
Wei, Dongshan
author_sort Xue, Qingming
collection PubMed
description BACKGROUND: LIM and SH3 domain protein 1 (LASP1), highly expressed in a variety of tumors, is considered as a novel tumor metastasis biomarker. However, it is unknown which signaling pathway works and how the signal transduces into cell nucleus to drive tumor progression by LASP1. The aim of this study is to explore the essential role of LASP1 in TGF-β1-induced epithelial-mesenchymal transition (EMT) in lung cancer cells. METHODS: The gene and protein levels of LASP-1 were successfully silenced or overexpressed by LASP-1 shRNA lentivirus or pcDNA in TGF-β1-treated lung cancer cell lines, respectively. Then, the cells were developed EMT by TGF-β1. The cell abilities of invasion, migration, and proliferation were measured using Transwell invasion assay, wound healing assay, and MTT assay, respectively. Western blotting was used to observe the protein levels of EMT-associated molecules, including N-cadherin, vimentin, and E-cadherin, and the key molecules in the TGF-β1/Smad/Snail signaling pathway, including pSmad2 and Smad2, pSmad3 and Smad3, and Smad7 in cell lysates, as well as Snail1, pSmad2, and pSmad3 in the nucleus. RESULTS: TGF-β1 induced higher LASP1 expression. LASP1 silence and overexpression blunted or promoted cell invasion, migration, and proliferation upon TGF-β1 stimulation. LASP1 also regulated the expression of vimentin, N-cadherin, and E-cadherin in TGF-β1-treated cells. Activity of key Smad proteins (pSmad2 and pSmad3) and protein level of Smad7 were markedly regulated through LASP1. Furthermore, LASP1 affected the nuclear localizations of pSmad2, pSmad3, and Snail1. CONCLUSION: This study reveals that LASP1 regulates the TGF-β1/Smad/Snail signaling pathway and EMT markers and features, involving in key signal molecules and their nuclear levels. Therefore, LASP1 might be a drug target in lung cancer.
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spelling pubmed-86682822021-12-14 LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway Xue, Qingming Jiang, Hong Wang, Jinjie Wei, Dongshan Can Respir J Research Article BACKGROUND: LIM and SH3 domain protein 1 (LASP1), highly expressed in a variety of tumors, is considered as a novel tumor metastasis biomarker. However, it is unknown which signaling pathway works and how the signal transduces into cell nucleus to drive tumor progression by LASP1. The aim of this study is to explore the essential role of LASP1 in TGF-β1-induced epithelial-mesenchymal transition (EMT) in lung cancer cells. METHODS: The gene and protein levels of LASP-1 were successfully silenced or overexpressed by LASP-1 shRNA lentivirus or pcDNA in TGF-β1-treated lung cancer cell lines, respectively. Then, the cells were developed EMT by TGF-β1. The cell abilities of invasion, migration, and proliferation were measured using Transwell invasion assay, wound healing assay, and MTT assay, respectively. Western blotting was used to observe the protein levels of EMT-associated molecules, including N-cadherin, vimentin, and E-cadherin, and the key molecules in the TGF-β1/Smad/Snail signaling pathway, including pSmad2 and Smad2, pSmad3 and Smad3, and Smad7 in cell lysates, as well as Snail1, pSmad2, and pSmad3 in the nucleus. RESULTS: TGF-β1 induced higher LASP1 expression. LASP1 silence and overexpression blunted or promoted cell invasion, migration, and proliferation upon TGF-β1 stimulation. LASP1 also regulated the expression of vimentin, N-cadherin, and E-cadherin in TGF-β1-treated cells. Activity of key Smad proteins (pSmad2 and pSmad3) and protein level of Smad7 were markedly regulated through LASP1. Furthermore, LASP1 affected the nuclear localizations of pSmad2, pSmad3, and Snail1. CONCLUSION: This study reveals that LASP1 regulates the TGF-β1/Smad/Snail signaling pathway and EMT markers and features, involving in key signal molecules and their nuclear levels. Therefore, LASP1 might be a drug target in lung cancer. Hindawi 2021-12-06 /pmc/articles/PMC8668282/ /pubmed/34912481 http://dx.doi.org/10.1155/2021/5277409 Text en Copyright © 2021 Qingming Xue et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Xue, Qingming
Jiang, Hong
Wang, Jinjie
Wei, Dongshan
LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway
title LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway
title_full LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway
title_fullStr LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway
title_full_unstemmed LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway
title_short LASP1 Induces Epithelial-Mesenchymal Transition in Lung Cancer through the TGF-β1/Smad/Snail Pathway
title_sort lasp1 induces epithelial-mesenchymal transition in lung cancer through the tgf-β1/smad/snail pathway
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8668282/
https://www.ncbi.nlm.nih.gov/pubmed/34912481
http://dx.doi.org/10.1155/2021/5277409
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