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Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer

A recent study indicated that high Wnt5a expression is associated with poor prognosis in non-small-cell lung cancer (NSCLC) patients; however, the underlying mechanism was not clear yet. Immunohistochemistry and Western blotting were performed to examine the protein expression level in NSCLC tissues...

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Autores principales: Wang, Biao, Tang, Zhen, Gong, Huiyuan, Zhu, Li, Liu, Xuegang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705780/
https://www.ncbi.nlm.nih.gov/pubmed/29054966
http://dx.doi.org/10.1042/BSR20171092
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author Wang, Biao
Tang, Zhen
Gong, Huiyuan
Zhu, Li
Liu, Xuegang
author_facet Wang, Biao
Tang, Zhen
Gong, Huiyuan
Zhu, Li
Liu, Xuegang
author_sort Wang, Biao
collection PubMed
description A recent study indicated that high Wnt5a expression is associated with poor prognosis in non-small-cell lung cancer (NSCLC) patients; however, the underlying mechanism was not clear yet. Immunohistochemistry and Western blotting were performed to examine the protein expression level in NSCLC tissues and cell lines. The role of Wnt5a in clone formation, invasiveness, migration, and epithelial-to-mesenchymal transition (EMT) of NSCLC cells was studied. Luciferase reporter assay was used to evaluate the Tcf/Lef transcriptional activity. For assessing the effects of Wnt5a on tumor growth and metastasis in vivo, A549 cells transfected with sh-Wnt5a were subcutaneously or orthotopically injected into nude mice. In NSCLC tissues, higher expression levels of Wnt5a and ROR2 were found, β-Catenin was expressed exceptionally, and EMT was prompted. Wnt5a overexpression increased clone formation, migration, and invasion, as well as prompted EMT of NSCLC cell in vitro, whereas Wnt5a knockdown showed the absolutely reversed results. Wnt5a overexpression enhanced the Tcf/Lef transcriptional activity and elevated the nuclear β-catenin level in NSCLC cells, without altering the ROR2 expression. We also demonstrated that si-β-catenin antagonized Wnt5a overexpression nduced EMT and invasiveness. Besides, in vivo experiment showed that sh-Wnt5a significantly increased tumor volume and tumor weight, and prompted EMT in A549 tumor-bearing mice as compared with the control. No metastasis was found in the liver tissue after sh-Wnt5a-transfected cells were orthotopically injected into nude mice as compared with the control. In conclusion, Wnt5a promotes EMT and metastasis in NSCLC, which is involved in the activation of β-catenin-dependent canonical Wnt signaling.
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spelling pubmed-57057802017-12-12 Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer Wang, Biao Tang, Zhen Gong, Huiyuan Zhu, Li Liu, Xuegang Biosci Rep Research Articles A recent study indicated that high Wnt5a expression is associated with poor prognosis in non-small-cell lung cancer (NSCLC) patients; however, the underlying mechanism was not clear yet. Immunohistochemistry and Western blotting were performed to examine the protein expression level in NSCLC tissues and cell lines. The role of Wnt5a in clone formation, invasiveness, migration, and epithelial-to-mesenchymal transition (EMT) of NSCLC cells was studied. Luciferase reporter assay was used to evaluate the Tcf/Lef transcriptional activity. For assessing the effects of Wnt5a on tumor growth and metastasis in vivo, A549 cells transfected with sh-Wnt5a were subcutaneously or orthotopically injected into nude mice. In NSCLC tissues, higher expression levels of Wnt5a and ROR2 were found, β-Catenin was expressed exceptionally, and EMT was prompted. Wnt5a overexpression increased clone formation, migration, and invasion, as well as prompted EMT of NSCLC cell in vitro, whereas Wnt5a knockdown showed the absolutely reversed results. Wnt5a overexpression enhanced the Tcf/Lef transcriptional activity and elevated the nuclear β-catenin level in NSCLC cells, without altering the ROR2 expression. We also demonstrated that si-β-catenin antagonized Wnt5a overexpression nduced EMT and invasiveness. Besides, in vivo experiment showed that sh-Wnt5a significantly increased tumor volume and tumor weight, and prompted EMT in A549 tumor-bearing mice as compared with the control. No metastasis was found in the liver tissue after sh-Wnt5a-transfected cells were orthotopically injected into nude mice as compared with the control. In conclusion, Wnt5a promotes EMT and metastasis in NSCLC, which is involved in the activation of β-catenin-dependent canonical Wnt signaling. Portland Press Ltd. 2017-11-29 /pmc/articles/PMC5705780/ /pubmed/29054966 http://dx.doi.org/10.1042/BSR20171092 Text en © 2017 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Wang, Biao
Tang, Zhen
Gong, Huiyuan
Zhu, Li
Liu, Xuegang
Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer
title Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer
title_full Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer
title_fullStr Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer
title_full_unstemmed Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer
title_short Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer
title_sort wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705780/
https://www.ncbi.nlm.nih.gov/pubmed/29054966
http://dx.doi.org/10.1042/BSR20171092
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