Just say no to ATOH: how HIC1 methylation might predispose medulloblastoma to lineage addiction

Cancer Res. 2008 Nov 1;68(21):8654-6. doi: 10.1158/0008-5472.CAN-08-1904.

Abstract

Hypermethylated in cancer-1 (HIC1) is a tumor suppressor frequently targeted for promoter hypermethylation in medulloblastoma, an embryonal tumor of the cerebellum. Recently, we showed that HIC1 is a direct transcriptional repressor of ATOH1, a proneural transcription factor required for normal cerebellar development, as well as for medulloblastoma cell viability. Because demethylating agents can induce reexpression of silenced tumor suppressors, restoring HIC1 function may present an attractive therapeutic avenue in medulloblastoma by exploiting an apparent addiction to ATOH1.

Publication types

  • Review

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Cell Lineage
  • Chromosome Deletion
  • Chromosomes, Human, Pair 17
  • DNA Methylation*
  • Epigenesis, Genetic
  • Gene Silencing
  • Genes, Tumor Suppressor
  • Humans
  • Kruppel-Like Transcription Factors / genetics
  • Kruppel-Like Transcription Factors / physiology*
  • Medulloblastoma / genetics*
  • Medulloblastoma / pathology

Substances

  • ATOH1 protein, human
  • Basic Helix-Loop-Helix Transcription Factors
  • HIC1 protein, human
  • Kruppel-Like Transcription Factors