[Show abstract][Hide abstract] ABSTRACT: Hypermethylated in cancer 1(HIC1) was identified as a strong suppressor gene in chromosome region 17p13.3 telomeric to TP53. This gene encodes a transcriptional repressor and is ubiquitously expressed in normal tissues but downexpressed in different tumor tissues where it is hypermethylated. The hypermethylation of this chromosomal region leads to epigenetic inactivation of HIC1, which would prompt cancer cells to alter survival and signaling pathways or specific transcription factors during the period of tumorigenesis. In vitro, HIC1 function is mainly a sequence-specific transcriptional repressor interacting with a still growing range of histone deacetylase(HDAC)-dependent and HDAC-independent corepressor complexes. Furthermore, a role for HIC1 in tumor development is firmly supported by Hic1 deficient mouse model and two double heterozygote models cooperate with p53 and Ptch1. Notably, our findings suggest that potential factors derived from tumor microenviroment may play a role in modulating HIC1 expression in tumor cells by epigenetic modification, which is responsible for tumor progression. In this review, we will describe genomic and proteinic structure of HIC1, and summary the potential role of HIC1 in human various solid tumors and leukemia, and explore the influence of tumor microenviroment on inducing HIC1 expression in tumor cells.