The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.

The transcriptional repressors Snail and Slug are situated at the core of several signaling pathways proposed to mediate epithelial to mesenchymal transition or EMT, which has been implicated in tumor metastasis. EMT involves an alteration from an organized, epithelial cell structure to a mesenchyma...

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Autores principales:	Archana Dhasarathy, Dhiral Phadke, Deepak Mav, Ruchir R Shah, Paul A Wade
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d2d91fe0a7134e46b0f1440415050e43
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spelling	oai:doaj.org-article:d2d91fe0a7134e46b0f1440415050e432021-11-18T07:36:01ZThe transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.1932-620310.1371/journal.pone.0026514https://doaj.org/article/d2d91fe0a7134e46b0f1440415050e432011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22028892/?tool=EBIhttps://doaj.org/toc/1932-6203The transcriptional repressors Snail and Slug are situated at the core of several signaling pathways proposed to mediate epithelial to mesenchymal transition or EMT, which has been implicated in tumor metastasis. EMT involves an alteration from an organized, epithelial cell structure to a mesenchymal, invasive and migratory phenotype. In order to obtain a global view of the impact of Snail and Slug expression, we performed a microarray experiment using the MCF-7 breast cancer cell line, which does not express detectable levels of Snail or Slug. MCF-7 cells were infected with Snail, Slug or control adenovirus, and RNA samples isolated at various time points were analyzed across all transcripts. Our analyses indicated that Snail and Slug regulate many genes in common, but also have distinct sets of gene targets. Gene set enrichment analyses indicated that Snail and Slug directed the transcriptome of MCF-7 cells from a luminal towards a more complex pattern that includes many features of the claudin-low breast cancer signature. Of particular interest, genes involved in the TGF-beta signaling pathway are upregulated, while genes responsible for a differentiated morphology are downregulated following Snail or Slug expression. Further we noticed increased histone acetylation at the promoter region of the transforming growth factor beta-receptor II (TGFBR2) gene following Snail or Slug expression. Inhibition of the TGF-beta signaling pathway using selective small-molecule inhibitors following Snail or Slug addition resulted in decreased cell migration with no impact on the repression of cell junction molecules by Snail and Slug. We propose that there are two regulatory modules embedded within EMT: one that involves repression of cell junction molecules, and the other involving cell migration via TGF-beta and/or other pathways.Archana DhasarathyDhiral PhadkeDeepak MavRuchir R ShahPaul A WadePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26514 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Archana Dhasarathy Dhiral Phadke Deepak Mav Ruchir R Shah Paul A Wade The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.
description	The transcriptional repressors Snail and Slug are situated at the core of several signaling pathways proposed to mediate epithelial to mesenchymal transition or EMT, which has been implicated in tumor metastasis. EMT involves an alteration from an organized, epithelial cell structure to a mesenchymal, invasive and migratory phenotype. In order to obtain a global view of the impact of Snail and Slug expression, we performed a microarray experiment using the MCF-7 breast cancer cell line, which does not express detectable levels of Snail or Slug. MCF-7 cells were infected with Snail, Slug or control adenovirus, and RNA samples isolated at various time points were analyzed across all transcripts. Our analyses indicated that Snail and Slug regulate many genes in common, but also have distinct sets of gene targets. Gene set enrichment analyses indicated that Snail and Slug directed the transcriptome of MCF-7 cells from a luminal towards a more complex pattern that includes many features of the claudin-low breast cancer signature. Of particular interest, genes involved in the TGF-beta signaling pathway are upregulated, while genes responsible for a differentiated morphology are downregulated following Snail or Slug expression. Further we noticed increased histone acetylation at the promoter region of the transforming growth factor beta-receptor II (TGFBR2) gene following Snail or Slug expression. Inhibition of the TGF-beta signaling pathway using selective small-molecule inhibitors following Snail or Slug addition resulted in decreased cell migration with no impact on the repression of cell junction molecules by Snail and Slug. We propose that there are two regulatory modules embedded within EMT: one that involves repression of cell junction molecules, and the other involving cell migration via TGF-beta and/or other pathways.
format	article
author	Archana Dhasarathy Dhiral Phadke Deepak Mav Ruchir R Shah Paul A Wade
author_facet	Archana Dhasarathy Dhiral Phadke Deepak Mav Ruchir R Shah Paul A Wade
author_sort	Archana Dhasarathy
title	The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.
title_short	The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.
title_full	The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.
title_fullStr	The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.
title_full_unstemmed	The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.
title_sort	transcription factors snail and slug activate the transforming growth factor-beta signaling pathway in breast cancer.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/d2d91fe0a7134e46b0f1440415050e43
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The transcription factors Snail and Slug activate the transforming growth factor-beta signaling pathway in breast cancer.

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