title: Deciphering HIC1 control pathways to reveal new avenues in cancer therapeutics.
abstract: BACKGROUND
  The tumor suppressor gene HIC1 (Hypermethylated in Cancer 1), which encodes a transcriptional repressor with multiple partners and multiple targets, is epigenetically silenced but not mutated in tumors. HIC1 has broad biological roles during normal development and is implicated in many canonical processes of cancer such as control of cell growth, cell survival upon genotoxic stress, cell migration, and motility.
  
  
  METHODS
  The HIC1 literature herein discussed includes its discovery as a candidate tumor suppressor gene hypermethylated or deleted in many human tumors, animal models establishing it as tumor suppressor gene, its role as a sequence-specific transcriptional repressor recruiting several chromatin regulatory complexes, its cognate target genes, and its functional roles in normal tissues. Finally, this review discusses how its loss of function contributes to the early steps in tumorigenesis.
  
  
  CONCLUSIONS
  Given HIC1's ability to direct repressive complexes to sequence-specific binding sites associated with its target genes, its loss results in specific changes in the transcriptional program of the cell. An understanding of this program through identification of HIC1's target genes and their involvement in feedback loops and cell process regulation will yield the ability to leverage this knowledge for therapeutic translation.
authors.affiliation: Center for Cancer and Blood Disorders, Children's National Medical Center, Division of Oncology, 111 Michigan Ave. NW, Washington, DC 20010, USA.
authors.forename: Brian R
authors.initials: BR
authors.lastname: Rood
authors.forename: Dominique
authors.initials: D
authors.lastname: Leprince
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D057890:Epigenomics; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: C499808:HIC1 protein, human; D051741:Kruppel-Like Transcription Factors; C447939:SIRT1 protein, human; D056564:Sirtuin 1