Histone deacetylases, Mbd3/NuRD, and Tet2 hydroxylase are crucial regulators of epithelial-mesenchymal plasticity and tumor metastasis

被引：19

作者：

Kilinc, Ayse Nihan ^{[1
,2
]}

Sugiyama, Nami ^{[1
]}

Kalathur, Ravi Kiran Reddy ^{[1
]}

Antoniadis, Helena ^{[1
]}

Birogul, Huseyin ^{[1
]}

Ishay-Ronen, Dana ^{[1
]}

George, Jason T. ^{[3
,4
]}

Levine, Herbert ^{[3
,5
,6
]}

Jolly, Mohit Kumar ^{[7
]}

Christofori, Gerhard ^{[1
]}

机构：

[1] Univ Basel, Dept Biomed, CH-4058 Basel, Switzerland

[2] Princeton Univ, Dept Chem & Biol Engn, 303 Hoyt Lab,William St, Princeton, NJ 08544 USA

[3] Rice Univ, Ctr Theoret Biol Phys, Houston, TX USA

[4] Baylor Coll Med, Med Sci Training Program, Houston, TX 77030 USA

[5] Northeastern Univ, Dept Bioengn, Boston, MA 02115 USA

[6] Northeastern Univ, Dept Phys, Boston, MA 02115 USA

[7] Indian Inst Sci, Ctr BioSyst Sci & Engn, Bangalore 560012, Karnataka, India

来源：

ONCOGENE | 2020年 / 39卷 / 07期

基金：

瑞士国家科学基金会;

关键词：

TRANSCRIPTION FACTOR SNAIL; CADHERIN GENE-EXPRESSION; MI-2/NURD COMPLEX; MASTER REGULATOR; CANCER-CELLS; TRANSITION; NURD; EMT; REPRESSOR; METHYLATION;

D O I：

10.1038/s41388-019-1081-2

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

An epithelial-mesenchymal transition (EMT) represents a basic morphogenetic process of high cell plasticity underlying embryogenesis, wound healing, cancer metastasis and drug resistance. It involves a profound transcriptional and epigenetic reprogramming of cells. A critical role of epigenetic modifiers and their specific chromatin modifications has been demonstrated during EMT. However, it has remained elusive whether epigenetic control differs between the dynamic cell state transitions of reversible EMT and the fixed differentiation status of irreversible EMT. We have employed varying EMT models of murine breast cancer cells to identify the key players establishing epithelial-mesenchymal cell plasticity during reversible and irreversible EMT. We demonstrate that the Mbd3/NuRD complex and the activities of histone deacetylases (HDACs), and Tet2 hydroxylase play a critical role in keeping cancer cells in a highly metastatic mesenchymal state. Combinatorial interference with their functions leads to mesenchymal-epithelial transition (MET) and efficiently represses metastasis formation by invasive murine and human breast cancer cells in vivo.

引用

页码：1498 / 1513

页数：16

共 61 条

[1] EMT Subtype Influences Epithelial Plasticity and Mode of Cell Migration [J].