Just say no to ATOH: how HIC1 methylation might predispose medulloblastoma to lineage addiction.
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.
Briggs
Kimberly J
KJ
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, USA.
Eberhart
Charles G
CG
Watkins
D Neil
DN
D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D019070:Cell Lineage; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000502:physiology*; D008527:Medulloblastoma / Q000235:genetics* / Q000473:pathology
D051792:Basic Helix-Loop-Helix Proteins; D051741:Kruppel-Like Transcription Factors; C500942:ATOH1 protein, human; C499808:HIC1 protein, human