Abstract 5603: Aryl hydrocarbon receptor, a receptor for environmental pollutants, promotes tumorigenesis via intestine-specific homeobox expression in hepatocellular carcinoma

Environmental pollutants often cause diseases. Aryl hydrocarbon receptor (AHR), a major transcriptional factor in the xenobiotic response, regulates cellular signaling and metabolism, thereby influencing disease progression. The detailed regulatory mechanisms, however, remain unclear. Here we demonstrate that AHR expression promotes tumorigenesis and is associated with shorter survival time in HCC patients. These phenomena appear to be mediated by activation of a target proto-oncogene, intestine-specific homeobox (ISX), in vitro and in vivo. The strong correlation of expression and cellular transcriptional regulation between AHR and ISX (in tumor and hepatoma cells) underscore the significant role of this duo in HCC tumorigenesis and prognosis. Our experiments with the ablation of ISX expression in AHR-mutant mice and hepatoma cells further support the essential roles of AHR and ISX in liver and tumor development. These results advance the understanding of the cellular function of AHR and of its downstream gene, ISX, in HCC progression. Our data may help to develop a new therapeutic approach to HCC. Citation Format: Li-Ting Wang, Shen-Nien Wang, Shih-Hsien Hsu. Aryl hydrocarbon receptor, a receptor for environmental pollutants, promotes tumorigenesis via intestine-specific homeobox expression in hepatocellular carcinoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5603. doi:10.1158/1538-7445.AM2014-5603