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CHD4 Has Oncogenic Functions in Initiating and Maintaining Epigenetic Suppression of Multiple Tumor Suppressor Genes.
- Source :
-
Cancer cell [Cancer Cell] 2017 May 08; Vol. 31 (5), pp. 653-668.e7. - Publication Year :
- 2017
-
Abstract
- An oncogenic role for CHD4, a NuRD component, is defined for initiating and supporting tumor suppressor gene (TSG) silencing in human colorectal cancer. CHD4 recruits repressive chromatin proteins to sites of DNA damage repair, including DNA methyltransferases where it imposes de novo DNA methylation. At TSGs, CHD4 retention helps maintain DNA hypermethylation-associated transcriptional silencing. CHD4 is recruited by the excision repair protein OGG1 for oxidative damage to interact with the damage-induced base 8-hydroxydeoxyguanosine (8-OHdG), while ZMYND8 recruits it to double-strand breaks. CHD4 knockdown activates silenced TSGs, revealing their role for blunting colorectal cancer cell proliferation, invasion, and metastases. High CHD4 and 8-OHdG levels plus low expression of TSGs strongly correlates with early disease recurrence and decreased overall survival.<br /> (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Subjects :
- 8-Hydroxy-2'-Deoxyguanosine
Animals
Autoantigens metabolism
Cell Movement
Cell Proliferation
Clustered Regularly Interspaced Short Palindromic Repeats
Colorectal Neoplasms enzymology
Colorectal Neoplasms pathology
Colorectal Neoplasms surgery
DNA (Cytosine-5-)-Methyltransferases genetics
DNA (Cytosine-5-)-Methyltransferases metabolism
DNA Damage
DNA Glycosylases genetics
DNA Glycosylases metabolism
Deoxyguanosine analogs & derivatives
Deoxyguanosine metabolism
Disease-Free Survival
Down-Regulation
Enhancer of Zeste Homolog 2 Protein genetics
Enhancer of Zeste Homolog 2 Protein metabolism
HCT116 Cells
Histocompatibility Antigens genetics
Histocompatibility Antigens metabolism
Histone-Lysine N-Methyltransferase genetics
Histone-Lysine N-Methyltransferase metabolism
Humans
Kaplan-Meier Estimate
Mi-2 Nucleosome Remodeling and Deacetylase Complex metabolism
Mice, Inbred BALB C
Mice, Nude
Neoplasm Metastasis
Oxidative Stress
Proportional Hazards Models
RNA Interference
Receptors for Activated C Kinase
Receptors, Cell Surface genetics
Receptors, Cell Surface metabolism
Time Factors
Transcription, Genetic
Transfection
Tumor Suppressor Proteins
Autoantigens genetics
Colorectal Neoplasms genetics
DNA Methylation
Epigenetic Repression
Gene Expression Regulation, Neoplastic
Gene Silencing
Genes, Tumor Suppressor
Mi-2 Nucleosome Remodeling and Deacetylase Complex genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1878-3686
- Volume :
- 31
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cancer cell
- Publication Type :
- Academic Journal
- Accession number :
- 28486105
- Full Text :
- https://doi.org/10.1016/j.ccell.2017.04.005