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Kaiso Contributes to DNA Methylation-Dependent Silencing of Tumor Suppressor Genes in Colon Cancer Cell Lines
Published version of a preprint
Abstract
Aberrant CpG methylation of tumor suppressor gene regulatory elements is associated with transcriptional silencing and contributes to malignant transformation of different tissues. It is presumed that methylated DNA sequences recruit repressor machinery to actively shutdown gene expression. The Kaiso protein is a transcriptional repressor expressed in human and murine colorectal tumors that can bind to methylated clusters of CpG dinucleotides. We show here that Kaiso represses methylated tumor suppressor genes and can bind in a methylation-dependent manner to the CDKN2A in human colon cancer cell lines. The contribution of Kaiso to epigenetic silencing was underlined by the fact that Kaiso depletion induced tumor suppressor gene expression without affecting DNA methylation levels. As a consequence, colon cancer cells became susceptible to cell cycle arrest and cell death mediated by chemotherapy. The data suggest that Kaiso is a methylation-dependent “opportunistic” oncogene that silences tumor suppressor genes when they become hypermethylated. Because Kaiso inactivation sensitized colon cancer cell lines to chemotherapy, it is possible that therapeutic targeting of Kaiso could improve the efficacy of current treatment regimens. [Cancer Res 2008;68(18):7258–63]
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“Kaiso binds to the methylated promoters of CDKN2A, MGMT and HIC1 in both HCT116 and Colo320 human colon cancer cell lines62.”
From Transcription factors as readers and effectors of DNA methylation (2016) · cites this paper as [62]
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Metadata
- Authors
- Lopes, E. C., Valls, E., Figueroa, M. E., Mazur, A., Meng, F.-G., Chiosis, G., Laird, P. W., Schreiber-Agus, N., Greally, J. M., Prokhortchouk, E., & Melnick, A.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- Yeshiva University (US)
- 2Division of Hematology and Medical Oncology, Weill Cornell Medical College, New York, New York; Departments of
- Bioengineering Center (RU)
- USC Norris Comprehensive Cancer Center (US)
- 4Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York;
- Albert Einstein College of Medicine (US)
- Venue
- Cancer Research
- Published
- 2008-09-14
- Volume
- 68
- Issue
- 18
- Pages
- 7258-7263
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2089255658
- Cited by
- 119
- References
- 30
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 3 · 2020: 4 · 2019: 11 · 2018: 4 · 2017: 7 · 2016: 11 · 2015: 6 · 2014: 8 · 2013: 5 · 2012: 14
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ca075090-09)
- National Cancer Institute (R01-CA-075090, R01CA118699)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer-related gene regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- Kaiso, DNA methylation, CpG methylation, tumor suppressor, transcriptional silencing, CDKN2A, colon cancer, epigenetic silencing, transcriptional repressor, cell cycle arrest, chemosensitivity, colorectal neoplasia
- MeSH terms
- Cell Cycle, Colonic Neoplasms, Humans, Promoter Regions, Genetic, Protein Binding, Transcription Factors, Transfection, Genes, Tumor Suppressor, Cell Death, DNA Methylation, Cyclin-Dependent Kinase Inhibitor p16, Genes, p16, Gene Silencing, RNA, Small Interfering, HCT116 Cells, Cell Line, Tumor
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