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Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters

BACKGROUND: Epithelial-mesenchymal transition (EMT) not only confers tumor cells with a distinct advantage for metastatic dissemination, but also it provides those cells with cancer stem cell-like characters for proliferation and drug resistance. However, the molecular mechanism for maintenance of t...

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Detalles Bibliográficos
Autores principales: Li, Junlin, Zhou, Binhua P
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040162/
https://www.ncbi.nlm.nih.gov/pubmed/21284870
http://dx.doi.org/10.1186/1471-2407-11-49
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author Li, Junlin
Zhou, Binhua P
author_facet Li, Junlin
Zhou, Binhua P
author_sort Li, Junlin
collection PubMed
description BACKGROUND: Epithelial-mesenchymal transition (EMT) not only confers tumor cells with a distinct advantage for metastatic dissemination, but also it provides those cells with cancer stem cell-like characters for proliferation and drug resistance. However, the molecular mechanism for maintenance of these stem cell-like traits remains unclear. METHODS: In this study, we induced EMT in breast cancer MCF7 and cervical cancer Hela cells with expression of Twist, a key transcriptional factor of EMT. The morphological changes associated with EMT were analyzed by immunofluorescent staining and Western blotting. The stem cell-like traits associated with EMT were determined by tumorsphere-formation and expression of ALDH1 and CD44 in these cells. The activation of β-catenin and Akt pathways was examined by Western blotting and luciferase assays. RESULTS: We found that expression of Twist induced a morphological change associated with EMT. We also found that the cancer stem cell-like traits, such as tumorsphere formation, expression of ALDH1 and CD44, were significantly elevated in Twist-overexpressing cells. Interestingly, we showed that β-catenin and Akt pathways were activated in these Twist-overexpressing cells. Activation of β-catenin correlated with the expression of CD44. Knockdown of β-catenin expression and inhibition of the Akt pathway greatly suppressed the expression of CD44. CONCLUSIONS: Our results indicate that activation of β-catenin and Akt pathways are required for the sustention of EMT-associated stem cell-like traits.
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spelling pubmed-30401622011-02-17 Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters Li, Junlin Zhou, Binhua P BMC Cancer Research Article BACKGROUND: Epithelial-mesenchymal transition (EMT) not only confers tumor cells with a distinct advantage for metastatic dissemination, but also it provides those cells with cancer stem cell-like characters for proliferation and drug resistance. However, the molecular mechanism for maintenance of these stem cell-like traits remains unclear. METHODS: In this study, we induced EMT in breast cancer MCF7 and cervical cancer Hela cells with expression of Twist, a key transcriptional factor of EMT. The morphological changes associated with EMT were analyzed by immunofluorescent staining and Western blotting. The stem cell-like traits associated with EMT were determined by tumorsphere-formation and expression of ALDH1 and CD44 in these cells. The activation of β-catenin and Akt pathways was examined by Western blotting and luciferase assays. RESULTS: We found that expression of Twist induced a morphological change associated with EMT. We also found that the cancer stem cell-like traits, such as tumorsphere formation, expression of ALDH1 and CD44, were significantly elevated in Twist-overexpressing cells. Interestingly, we showed that β-catenin and Akt pathways were activated in these Twist-overexpressing cells. Activation of β-catenin correlated with the expression of CD44. Knockdown of β-catenin expression and inhibition of the Akt pathway greatly suppressed the expression of CD44. CONCLUSIONS: Our results indicate that activation of β-catenin and Akt pathways are required for the sustention of EMT-associated stem cell-like traits. BioMed Central 2011-02-01 /pmc/articles/PMC3040162/ /pubmed/21284870 http://dx.doi.org/10.1186/1471-2407-11-49 Text en Copyright ©2011 Li and Zhou; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Junlin
Zhou, Binhua P
Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters
title Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters
title_full Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters
title_fullStr Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters
title_full_unstemmed Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters
title_short Activation of β-catenin and Akt pathways by Twist are critical for the maintenance of EMT associated cancer stem cell-like characters
title_sort activation of β-catenin and akt pathways by twist are critical for the maintenance of emt associated cancer stem cell-like characters
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3040162/
https://www.ncbi.nlm.nih.gov/pubmed/21284870
http://dx.doi.org/10.1186/1471-2407-11-49
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