Sorafenib Inhibits Epithelial-Mesenchymal Transition through an Epigenetic-Based Mechanism in Human Lung Epithelial Cells

	Sorafenib Inhibits Epithelial-Mesenchymal Transition through an Epigenetic-Based Mechanism in Human Lung Epithelial Cells
	Zhang, JY; Chen, YL; Ji, GY; Fang, WY; Gao, ZW; Liu, Y; Wang, J; Ding, XY; Gao, F
刊名	PLOS ONE
	2013
卷号	8 期号:5 页码:42005
通讯作者	Ding, XY (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai, Peoples R China.,xyding@sunm.shcnc.ac.cn ; gaofei@genomics.org.cn
英文摘要	The epithelial to mesenchymal transition (EMT) has been well recognized for many decades as an essential early step in the progression of primary tumors towards metastases. Widespread epigenetic reprogramming of DNA and histone modifications tightly regulates gene expression and cellular activity during carcinogenesis, and epigenetic therapy has been developed to design efficient strategies for cancer treatment. As the first oral agent approved for the clinical treatment of cancer, sorafenib has significant inhibitory effects on tumor growth and EMT. However, a detailed understanding of the underlying epigenetic mechanism remains elusive. In this manuscript, we performed a ChIP-seq assay to evaluate the activity of sorafenib on the genome-wide profiling of histone modifications. We demonstrate that sorafenib largely reverses the changes in histone modifications that occur during EMT in A549 alveolar epithelial cells. Sorafenib also significantly reduces the coordinated epigenetic switching of critical EMT-associated genes in accordance with their expression levels. Furthermore, we show that sorafenib potentiates histone acetylation by regulating the expression levels of histone-modifying enzymes. Collectively, these findings provide the first evidence that sorafenib inhibits the EMT process through an epigenetic mechanism, which holds enormous promise for identifying novel epigenetic candidate diagnostic markers and drug targets for the treatment of human malignancies.
学科主题	Science & Technology - Other Topics
类目[WOS]	Multidisciplinary Sciences
关键词[WOS]	HISTONE DEACETYLASE INHIBITORS ; E-CADHERIN ; HEPATOCELLULAR-CARCINOMA ; TGF-BETA ; TUMOR PROGRESSION ; CANCER ; METHYLATION ; COMBINATION ; EXPRESSION ; REPRESSION
收录类别	SCI
语种	英语
WOS记录号	WOS:000319799900147
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/386]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Zhang, JY,Chen, YL,Ji, GY,et al. Sorafenib Inhibits Epithelial-Mesenchymal Transition through an Epigenetic-Based Mechanism in Human Lung Epithelial Cells[J]. PLOS ONE,2013,8(5):42005.
APA	Zhang, JY.,Chen, YL.,Ji, GY.,Fang, WY.,Gao, ZW.,...&Gao, F.(2013).Sorafenib Inhibits Epithelial-Mesenchymal Transition through an Epigenetic-Based Mechanism in Human Lung Epithelial Cells.PLOS ONE,8(5),42005.
MLA	Zhang, JY,et al."Sorafenib Inhibits Epithelial-Mesenchymal Transition through an Epigenetic-Based Mechanism in Human Lung Epithelial Cells".PLOS ONE 8.5(2013):42005.