Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming

Neha Tiwari; Vijay K Tiwari; Lorenz Waldmeier; Piotr J Balwierz; Phil Arnold; Mikhail Pachkov; Nathalie Meyer-Schaller; Dirk Schübeler; Erik van Nimwegen; Gerhard Christofori

doi:10.1016/j.ccr.2013.04.020

Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming

Neha Tiwari, Vijay K Tiwari, Lorenz Waldmeier, Piotr J Balwierz, Phil Arnold, Mikhail Pachkov, Nathalie Meyer-Schaller, Dirk Schübeler, Erik van Nimwegen, Gerhard Christofori

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

Abstract

Gene expression profiling has uncovered the transcription factor Sox4 with upregulated activity during TGF-β-induced epithelial-mesenchymal transition (EMT) in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, whereas forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2.

Originalsprog	Engelsk
Tidsskrift	Cancer Cell
Vol/bind	23
Udgave nummer	6
Sider (fra-til)	768-783
ISSN	1535-6108
DOI	https://doi.org/10.1016/j.ccr.2013.04.020
Status	Udgivet - 10. jun. 2013
Udgivet eksternt	Ja

Bibliografisk note

Dokumenter og links

10.1016/j.ccr.2013.04.020

Citationsformater

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title = "Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming",

abstract = "Gene expression profiling has uncovered the transcription factor Sox4 with upregulated activity during TGF-β-induced epithelial-mesenchymal transition (EMT) in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, whereas forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2.",

keywords = "Animals, Cell Line, Cell Movement/genetics, Cell Survival/genetics, Enhancer of Zeste Homolog 2 Protein, Epigenesis, Genetic, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Histones/metabolism, Humans, MCF-7 Cells, Mammary Neoplasms, Experimental/genetics, Methylation, Mice, Neoplasm Metastasis/genetics, Polycomb Repressive Complex 2/genetics, Promoter Regions, Genetic, SOXC Transcription Factors/genetics, Transcription, Genetic",

author = "Neha Tiwari and Tiwari, {Vijay K} and Lorenz Waldmeier and Balwierz, {Piotr J} and Phil Arnold and Mikhail Pachkov and Nathalie Meyer-Schaller and Dirk Sch{\"u}beler and {van Nimwegen}, Erik and Gerhard Christofori",

year = "2013",

month = jun,

day = "10",

doi = "10.1016/j.ccr.2013.04.020",

language = "English",

volume = "23",

pages = "768--783",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

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TY - JOUR

T1 - Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming

AU - Tiwari, Neha

AU - Tiwari, Vijay K

AU - Waldmeier, Lorenz

AU - Balwierz, Piotr J

AU - Arnold, Phil

AU - Pachkov, Mikhail

AU - Meyer-Schaller, Nathalie

AU - Schübeler, Dirk

AU - van Nimwegen, Erik

AU - Christofori, Gerhard

PY - 2013/6/10

Y1 - 2013/6/10

N2 - Gene expression profiling has uncovered the transcription factor Sox4 with upregulated activity during TGF-β-induced epithelial-mesenchymal transition (EMT) in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, whereas forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2.

AB - Gene expression profiling has uncovered the transcription factor Sox4 with upregulated activity during TGF-β-induced epithelial-mesenchymal transition (EMT) in normal and cancerous breast epithelial cells. Sox4 is indispensable for EMT and cell survival in vitro and for primary tumor growth and metastasis in vivo. Among several EMT-relevant genes, Sox4 directly regulates the expression of Ezh2, encoding the Polycomb group histone methyltransferase that trimethylates histone 3 lysine 27 (H3K27me3) for gene repression. Ablation of Ezh2 expression prevents EMT, whereas forced expression of Ezh2 restores EMT in Sox4-deficient cells. Ezh2-mediated H3K27me3 marks associate with key EMT genes, representing an epigenetic EMT signature that predicts patient survival. Our results identify Sox4 as a master regulator of EMT by governing the expression of the epigenetic modifier Ezh2.

KW - Animals

KW - Cell Line

KW - Cell Movement/genetics

KW - Cell Survival/genetics

KW - Enhancer of Zeste Homolog 2 Protein

KW - Epigenesis, Genetic

KW - Epithelial-Mesenchymal Transition

KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Histones/metabolism

KW - Humans

KW - MCF-7 Cells

KW - Mammary Neoplasms, Experimental/genetics

KW - Methylation

KW - Mice

KW - Neoplasm Metastasis/genetics

KW - Polycomb Repressive Complex 2/genetics

KW - Promoter Regions, Genetic

KW - SOXC Transcription Factors/genetics

KW - Transcription, Genetic

U2 - 10.1016/j.ccr.2013.04.020

DO - 10.1016/j.ccr.2013.04.020

M3 - Journal article

C2 - 23764001

SN - 1535-6108

VL - 23

SP - 768

EP - 783

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming

Abstract

Bibliografisk note

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