SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.

The epithelial to mensenchymal transition program regulates various aspects of embryonic development and tissue homeostasis, but aberrant activation of this pathway in cancer contributes to tumor progression and metastasis. TGF-b potently induces an epithelial to mensenchymal transition in cancers o...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Stephin J Vervoort, Ana Rita Lourenço, Ruben van Boxtel, Paul J Coffer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a22ca4ae88e347cf911200bf37137ff5
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a22ca4ae88e347cf911200bf37137ff5
record_format	dspace
spelling	oai:doaj.org-article:a22ca4ae88e347cf911200bf37137ff52021-11-18T08:02:46ZSOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.1932-620310.1371/journal.pone.0053238https://doaj.org/article/a22ca4ae88e347cf911200bf37137ff52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23301048/?tool=EBIhttps://doaj.org/toc/1932-6203The epithelial to mensenchymal transition program regulates various aspects of embryonic development and tissue homeostasis, but aberrant activation of this pathway in cancer contributes to tumor progression and metastasis. TGF-b potently induces an epithelial to mensenchymal transition in cancers of epithelial origin by inducing transcriptional changes mediated by several key transcription factors. Here, we identify the developmental transcription factor SOX4 as a transcriptional target of TGF-b in immortalized human mammary epithelial cells. SOX4 expression and activity are rapidly induced in the early stages of the TGF-b-induced epithelial to mensenchymal transition. We demonstrate that conditional activation of Sox4 is sufficient to induce the expression of N-cadherin and additional mesenchymal markers including vimentin and fibronectin, but fails to induce complete EMT as no changes are observed in the expression of E-cadherin and b-catenin. Moreover, shRNA-mediated knockdown of SOX4 significantly delays TGF-b-induced mRNA and protein expression of mesenchymal markers. Taken together, these data suggest that TGF-b-mediated increased expression of SOX4 is required for the induction of a mesenchymal phenotype during EMT in human mammary epithelial cells.Stephin J VervoortAna Rita LourençoRuben van BoxtelPaul J CofferPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 1, p e53238 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stephin J Vervoort Ana Rita Lourenço Ruben van Boxtel Paul J Coffer SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.
description	The epithelial to mensenchymal transition program regulates various aspects of embryonic development and tissue homeostasis, but aberrant activation of this pathway in cancer contributes to tumor progression and metastasis. TGF-b potently induces an epithelial to mensenchymal transition in cancers of epithelial origin by inducing transcriptional changes mediated by several key transcription factors. Here, we identify the developmental transcription factor SOX4 as a transcriptional target of TGF-b in immortalized human mammary epithelial cells. SOX4 expression and activity are rapidly induced in the early stages of the TGF-b-induced epithelial to mensenchymal transition. We demonstrate that conditional activation of Sox4 is sufficient to induce the expression of N-cadherin and additional mesenchymal markers including vimentin and fibronectin, but fails to induce complete EMT as no changes are observed in the expression of E-cadherin and b-catenin. Moreover, shRNA-mediated knockdown of SOX4 significantly delays TGF-b-induced mRNA and protein expression of mesenchymal markers. Taken together, these data suggest that TGF-b-mediated increased expression of SOX4 is required for the induction of a mesenchymal phenotype during EMT in human mammary epithelial cells.
format	article
author	Stephin J Vervoort Ana Rita Lourenço Ruben van Boxtel Paul J Coffer
author_facet	Stephin J Vervoort Ana Rita Lourenço Ruben van Boxtel Paul J Coffer
author_sort	Stephin J Vervoort
title	SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.
title_short	SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.
title_full	SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.
title_fullStr	SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.
title_full_unstemmed	SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.
title_sort	sox4 mediates tgf-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a22ca4ae88e347cf911200bf37137ff5
work_keys_str_mv	AT stephinjvervoort sox4mediatestgfbinducedexpressionofmesenchymalmarkersduringmammarycellepithelialtomesenchymaltransition AT anaritalourenco sox4mediatestgfbinducedexpressionofmesenchymalmarkersduringmammarycellepithelialtomesenchymaltransition AT rubenvanboxtel sox4mediatestgfbinducedexpressionofmesenchymalmarkersduringmammarycellepithelialtomesenchymaltransition AT pauljcoffer sox4mediatestgfbinducedexpressionofmesenchymalmarkersduringmammarycellepithelialtomesenchymaltransition
_version_	1718422620687302656

SOX4 mediates TGF-β-induced expression of mesenchymal markers during mammary cell epithelial to mesenchymal transition.

Ejemplares similares