DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells

Adone Mohd-Sarip; Miriam Teeuwssen; Alice G. Bot; Maria J. De Herdt; Stefan M. Willems; Robert J. Baatenburg de Jong; Leendert H.J. Looijenga; Diana Zatreanu; Karel Bezstarosti; Job van Riet; Edwin Oole; Wilfred F.J. van Ijcken; Harmen J.G. van de Werken; Jeroen A. Demmers; Riccardo Fodde; C. Peter Verrijzer

doi:10.1016/j.celrep.2017.06.020

Cell Reports (Jul 2017)

DOC1-Dependent Recruitment of NURD Reveals Antagonism with SWI/SNF during Epithelial-Mesenchymal Transition in Oral Cancer Cells

Adone Mohd-Sarip,
Miriam Teeuwssen,
Alice G. Bot,
Maria J. De Herdt,
Stefan M. Willems,
Robert J. Baatenburg de Jong,
Leendert H.J. Looijenga,
Diana Zatreanu,
Karel Bezstarosti,
Job van Riet,
Edwin Oole,
Wilfred F.J. van Ijcken,
Harmen J.G. van de Werken,
Jeroen A. Demmers,
Riccardo Fodde,
C. Peter Verrijzer

Affiliations

Adone Mohd-Sarip: Centre for Cancer Research and Cell Biology, Queen’s University Belfast, Belfast BT9 7BL, UK, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Miriam Teeuwssen: Department of Pathology, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Alice G. Bot: Department of Biochemistry, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Maria J. De Herdt: Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Stefan M. Willems: Department of Pathology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, the Netherlands
Robert J. Baatenburg de Jong: Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Leendert H.J. Looijenga: Department of Pathology, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Diana Zatreanu: Department of Biochemistry, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Karel Bezstarosti: Proteomics Centre, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Job van Riet: Cancer Computational Biology Center, Erasmus MC Cancer Institute, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Edwin Oole: Center for Biomics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Wilfred F.J. van Ijcken: Center for Biomics, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Harmen J.G. van de Werken: Cancer Computational Biology Center, Erasmus MC Cancer Institute, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Jeroen A. Demmers: Proteomics Centre, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
Riccardo Fodde: Department of Pathology, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands
C. Peter Verrijzer: Department of Biochemistry, Erasmus University Medical Center, P.O. Box 1738, 3000 DR, Rotterdam, the Netherlands

DOI: https://doi.org/10.1016/j.celrep.2017.06.020
Journal volume & issue: Vol. 20, no. 1
pp. 61 – 75

Abstract

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The Nucleosome Remodeling and Deacetylase (NURD) complex is a key regulator of cell differentiation that has also been implicated in tumorigenesis. Loss of the NURD subunit Deleted in Oral Cancer 1 (DOC1) is associated with human oral squamous cell carcinomas (OSCCs). Here, we show that restoration of DOC1 expression in OSCC cells leads to a reversal of epithelial-mesenchymal transition (EMT). This is caused by the DOC1-dependent targeting of NURD to repress key transcriptional regulators of EMT. NURD recruitment drives extensive epigenetic reprogramming, including eviction of the SWI/SNF remodeler, formation of inaccessible chromatin, H3K27 deacetylation, and binding of PRC2 and KDM1A, followed by H3K27 methylation and H3K4 demethylation. Strikingly, depletion of SWI/SNF mimics the effects of DOC1 re-expression. Our results suggest that SWI/SNF and NURD function antagonistically to control chromatin state and transcription. We propose that disturbance of this dynamic equilibrium may lead to defects in gene expression that promote oncogenesis.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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