Systematic name M7371
Brief description Genes methylated aberrantly in HCT116 and Colo320 (colon cancer) cells.
Full description or 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.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18794111   Authors: Lopes EC,Valls E,Figueroa ME,Mazur A,Meng FG,Chiosis G,Laird PW,Schreiber-Agus N,Greally JM,Prokhortchouk E,Melnick A
Exact source Fig 2S: red or yellow in H and C
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Source species Homo sapiens
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