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Disabled-2 downregulation promotes epithelial-to-mesenchymal transition

BACKGROUND: Metastatic tumour cells are characterised by acquisition of migratory and invasive properties; properties shared by cells, which have undergone epithelial-to-mesenchymal transition (EMT). Disabled-2 (Dab2) is a putative tumour suppressor whose expression has been shown to be downregulate...

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Autores principales: Martin, J C, Herbert, B-S, Hocevar, B A
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994233/
https://www.ncbi.nlm.nih.gov/pubmed/21063401
http://dx.doi.org/10.1038/sj.bjc.6605975
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author Martin, J C
Herbert, B-S
Hocevar, B A
author_facet Martin, J C
Herbert, B-S
Hocevar, B A
author_sort Martin, J C
collection PubMed
description BACKGROUND: Metastatic tumour cells are characterised by acquisition of migratory and invasive properties; properties shared by cells, which have undergone epithelial-to-mesenchymal transition (EMT). Disabled-2 (Dab2) is a putative tumour suppressor whose expression has been shown to be downregulated in various cancer types including breast cancer; however, its exact function in suppressing tumour initiation or progression is unclear. METHODS: Disabled-2 isoform expression was determined by RT–PCR analysis in human normal and breast tumour samples. Using shRNA-mediated technology, Dab2 was stably downregulated in two cell model systems representing nontumourigenic human mammary epithelial cells. These cells were characterised for expression of EMT markers by RT–PCR and western blot analysis. RESULTS: Decreased expression of the p96 and p67 isoforms of Dab2 is observed in human breast tumour samples in comparison to normal human breast tissue. Decreased Dab2 expression in normal mammary epithelial cells leads to the appearance of a constitutive EMT phenotype. Disabled-2 downregulation leads to increased Ras/MAPK signalling, which facilitates the establishment of an autocrine transforming growth factor β (TGFβ) signalling loop, concomitant with increased expression of the TGFβ2 isoform. CONCLUSION: Loss of Dab2 expression, commonly observed in breast cancer, may facilitate TGFβ-stimulated EMT, and therefore increase the propensity for metastasis.
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spelling pubmed-29942332011-11-01 Disabled-2 downregulation promotes epithelial-to-mesenchymal transition Martin, J C Herbert, B-S Hocevar, B A Br J Cancer Molecular Diagnostics BACKGROUND: Metastatic tumour cells are characterised by acquisition of migratory and invasive properties; properties shared by cells, which have undergone epithelial-to-mesenchymal transition (EMT). Disabled-2 (Dab2) is a putative tumour suppressor whose expression has been shown to be downregulated in various cancer types including breast cancer; however, its exact function in suppressing tumour initiation or progression is unclear. METHODS: Disabled-2 isoform expression was determined by RT–PCR analysis in human normal and breast tumour samples. Using shRNA-mediated technology, Dab2 was stably downregulated in two cell model systems representing nontumourigenic human mammary epithelial cells. These cells were characterised for expression of EMT markers by RT–PCR and western blot analysis. RESULTS: Decreased expression of the p96 and p67 isoforms of Dab2 is observed in human breast tumour samples in comparison to normal human breast tissue. Decreased Dab2 expression in normal mammary epithelial cells leads to the appearance of a constitutive EMT phenotype. Disabled-2 downregulation leads to increased Ras/MAPK signalling, which facilitates the establishment of an autocrine transforming growth factor β (TGFβ) signalling loop, concomitant with increased expression of the TGFβ2 isoform. CONCLUSION: Loss of Dab2 expression, commonly observed in breast cancer, may facilitate TGFβ-stimulated EMT, and therefore increase the propensity for metastasis. Nature Publishing Group 2010-11 2010-11-09 /pmc/articles/PMC2994233/ /pubmed/21063401 http://dx.doi.org/10.1038/sj.bjc.6605975 Text en Copyright © 2010 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Molecular Diagnostics
Martin, J C
Herbert, B-S
Hocevar, B A
Disabled-2 downregulation promotes epithelial-to-mesenchymal transition
title Disabled-2 downregulation promotes epithelial-to-mesenchymal transition
title_full Disabled-2 downregulation promotes epithelial-to-mesenchymal transition
title_fullStr Disabled-2 downregulation promotes epithelial-to-mesenchymal transition
title_full_unstemmed Disabled-2 downregulation promotes epithelial-to-mesenchymal transition
title_short Disabled-2 downregulation promotes epithelial-to-mesenchymal transition
title_sort disabled-2 downregulation promotes epithelial-to-mesenchymal transition
topic Molecular Diagnostics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2994233/
https://www.ncbi.nlm.nih.gov/pubmed/21063401
http://dx.doi.org/10.1038/sj.bjc.6605975
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