Deciphering HIC1 control pathways to reveal new avenues in cancer therapeutics. (October 2013)

• Record Type: Journal Article
• Authors: Rood, Brian R; Leprince, Dominique
• Is Part Of: Expert opinion on therapeutic targets. Volume 17:Number 7(2013:Jul.)
• Page Start: 811
• Page End: 827
• Publication Date: 2013-10
• Subjects: Drugs -- Research -- Periodicals; 615.072
• DOI: 10.1517/14728222.2013.788152
• Languages: English
• ISSNs: 1744-7631

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold> <italic>Introduction:</italic> </bold> The tumor suppressor gene <italic>HIC1</italic> (<italic>Hypermethylated in Cancer 1</italic>), 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.</p> <p> <bold> <italic>Areas covered:</italic> </bold> The <italic>HIC1</italic> 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.</p> <p> <bold> <italic>Expert opinion:</italic> </bold> 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.</p> </abstract>