DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening

Abstract Increasing matrix stiffness caused by the extracellular matrix (ECM) deposition surrounding cancer cells is accompanied by epithelial–mesenchymal transition (EMT). Here, we show that expression levels of EMT marker genes along with discoidin domain receptor 2 (DDR2) can increase upon matrix...

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Autores principales:	Daehwan Kim, Eunae You, Jangho Jeong, Panseon Ko, Jung-Woong Kim, Sangmyung Rhee
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e69f12ac61974286a15a145bc34d635f
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spelling	oai:doaj.org-article:e69f12ac61974286a15a145bc34d635f2021-12-02T16:06:49ZDDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening10.1038/s41598-017-07126-72045-2322https://doaj.org/article/e69f12ac61974286a15a145bc34d635f2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07126-7https://doaj.org/toc/2045-2322Abstract Increasing matrix stiffness caused by the extracellular matrix (ECM) deposition surrounding cancer cells is accompanied by epithelial–mesenchymal transition (EMT). Here, we show that expression levels of EMT marker genes along with discoidin domain receptor 2 (DDR2) can increase upon matrix stiffening. DDR2 silencing by short hairpin RNA downregulated EMT markers. Promoter analysis and chromatin immunoprecipitation revealed that c-Myb and LEF1 may be responsible for DDR2 induction during cell culture on a stiff matrix. Mechanistically, c-Myb acetylation by p300, which is upregulated on the stiff matrix, seems to be necessary for the c-Myb-and-LEF1–mediated DDR2 expression. Finally, we found that the c-Myb–DDR2 axis is crucial for lung cancer cell line proliferation and expression of EMT marker genes in a stiff environment. Thus, our results suggest that DDR2 regulation by p300 expression and/or c-Myb acetylation upon matrix stiffening may be necessary for regulation of EMT and invasiveness of lung cancer cells.Daehwan KimEunae YouJangho JeongPanseon KoJung-Woong KimSangmyung RheeNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daehwan Kim Eunae You Jangho Jeong Panseon Ko Jung-Woong Kim Sangmyung Rhee DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening
description	Abstract Increasing matrix stiffness caused by the extracellular matrix (ECM) deposition surrounding cancer cells is accompanied by epithelial–mesenchymal transition (EMT). Here, we show that expression levels of EMT marker genes along with discoidin domain receptor 2 (DDR2) can increase upon matrix stiffening. DDR2 silencing by short hairpin RNA downregulated EMT markers. Promoter analysis and chromatin immunoprecipitation revealed that c-Myb and LEF1 may be responsible for DDR2 induction during cell culture on a stiff matrix. Mechanistically, c-Myb acetylation by p300, which is upregulated on the stiff matrix, seems to be necessary for the c-Myb-and-LEF1–mediated DDR2 expression. Finally, we found that the c-Myb–DDR2 axis is crucial for lung cancer cell line proliferation and expression of EMT marker genes in a stiff environment. Thus, our results suggest that DDR2 regulation by p300 expression and/or c-Myb acetylation upon matrix stiffening may be necessary for regulation of EMT and invasiveness of lung cancer cells.
format	article
author	Daehwan Kim Eunae You Jangho Jeong Panseon Ko Jung-Woong Kim Sangmyung Rhee
author_facet	Daehwan Kim Eunae You Jangho Jeong Panseon Ko Jung-Woong Kim Sangmyung Rhee
author_sort	Daehwan Kim
title	DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening
title_short	DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening
title_full	DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening
title_fullStr	DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening
title_full_unstemmed	DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening
title_sort	ddr2 controls the epithelial-mesenchymal-transition-related gene expression via c-myb acetylation upon matrix stiffening
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e69f12ac61974286a15a145bc34d635f
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DDR2 controls the epithelial-mesenchymal-transition-related gene expression via c-Myb acetylation upon matrix stiffening

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