Dynamic Chromatin Modification Sustains Epithelial-Mesenchymal Transition following Inducible Expression of Snail-1

被引：80

作者：

Javaid, Sarah ^{[1
,2
]}

Zhang, Jianmin ^{[1
,2
]}

Anderssen, Endre ^{[1
,2
]}

Black, Josh C. ^{[1
,2
]}

Wittner, Ben S. ^{[1
,2
]}

Tajima, Ken ^{[1
,2
]}

Ting, David T. ^{[1
,2
]}

Smolen, Gromoslaw A. ^{[1
,2
]}

Zubrowski, Matthew ^{[1
,2
]}

Desai, Rushil ^{[1
,2
]}

Maheswaran, Shyamala ^{[1
,2
]}

Ramaswamy, Sridhar ^{[1
,2
]}

Whetstine, Johnathan R. ^{[1
,2
]}

Haber, Daniel A. ^{[1
,2
,3
]}

机构：

[1] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA

[2] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

[3] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

CELL REPORTS | 2013年 / 5卷 / 06期

关键词：

TRANSCRIPTION FACTOR SNAIL; E-CADHERIN REPRESSION; STEM-CELLS; MIR-200; FAMILY; CANCER; METASTASIS; PROGRESSION; BREAST; CYCLE; PLURIPOTENCY;

D O I：

10.1016/j.celrep.2013.11.034

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Epithelial-mesenchymal transition (EMT) is thought to contribute to cancer metastasis, but its underlying mechanisms are not well understood. To define early steps in this cellular transformation, we analyzed human mammary epithelial cells with tightly regulated expression of Snail-1, a master regulator of EMT. After Snail-1 induction, epithelial markers were repressed within 6 hr, and mesenchymal genes were induced at 24 hr. Snail-1 binding to its target promoters was transient (6-48 hr) despite continued protein expression, and it was followed by both transient and long-lasting chromatin changes. Pharmacological inhibition of selected histone acetylation and demethylation pathways suppressed the induction as well as the maintenance of Snail-1-mediated EMT. Thus, EMT involves an epigenetic switch that may be prevented or reversed with the use of small-molecule inhibitors of chromatin modifiers.

引用

页码：1679 / 1689

页数：11

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