Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines

Eloisi C. Lopes, Ester Valls, Maria E. Figueroa, Alexander Mazur, Fan Guo Meng, Gabriela Chiosis, Peter W. Laird, Nicole Schreiber-Agus, John M. Greally, Egor Prokhortchouk, Ari Melnick

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)7258-7263
Number of pages6
JournalCancer Research
Volume68
Issue number18
DOIs
StatePublished - Sep 15 2008

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DNA Methylation
Tumor Suppressor Genes
Colonic Neoplasms
Methylation
Cell Line
Gene Expression
Drug Therapy
CpG Islands
Cell Cycle Checkpoints
Oncogenes
Epigenomics
Colorectal Neoplasms
Cell Death
Proteins
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lopes, E. C., Valls, E., Figueroa, M. E., Mazur, A., Meng, F. G., Chiosis, G., ... Melnick, A. (2008). Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines. Cancer Research, 68(18), 7258-7263. https://doi.org/10.1158/0008-5472.CAN-08-0344

Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines. / Lopes, Eloisi C.; Valls, Ester; Figueroa, Maria E.; Mazur, Alexander; Meng, Fan Guo; Chiosis, Gabriela; Laird, Peter W.; Schreiber-Agus, Nicole; Greally, John M.; Prokhortchouk, Egor; Melnick, Ari.

In: Cancer Research, Vol. 68, No. 18, 15.09.2008, p. 7258-7263.

Research output: Contribution to journalArticle

Lopes, EC, Valls, E, Figueroa, ME, Mazur, A, Meng, FG, Chiosis, G, Laird, PW, Schreiber-Agus, N, Greally, JM, Prokhortchouk, E & Melnick, A 2008, 'Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines', Cancer Research, vol. 68, no. 18, pp. 7258-7263. https://doi.org/10.1158/0008-5472.CAN-08-0344
Lopes, Eloisi C. ; Valls, Ester ; Figueroa, Maria E. ; Mazur, Alexander ; Meng, Fan Guo ; Chiosis, Gabriela ; Laird, Peter W. ; Schreiber-Agus, Nicole ; Greally, John M. ; Prokhortchouk, Egor ; Melnick, Ari. / Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines. In: Cancer Research. 2008 ; Vol. 68, No. 18. pp. 7258-7263.
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