HNF4α is a target of the Wnt/β-catenin pathway and regulates colorectal carcinogenesis

Abstract

Hepatocyte nuclear factor 4alpha (HNFalpha) is a transcription factor involved in liver function. Dysregulation of HNF4alpha leads to hepatocarcinogenesis. However, the role and mechanism of HNF4alpha; in colorectal cancer is still unknown. Here we demonstrate that HNF4alpha is upregulated in colorectal cancers. and HNF4alpha upregulation promotes colorectal tumorigenesis. Notably, expression levels of HNF4alpha are positively correlated with the Wnt/beta-catenin signaling pathway in colorectal cancer patients. Further, we showed that HNF4alpha is transcriptionally activated by Wnt/beta-catenin/TCF3 and is at least partially responsible for the oncognesis activity of the Wnt signaling in colorectal cancer. Our findings indicate that HNF4alpha is a direct target of that Wnt/beta-catenin pathway and could play an important role in colorectal carcinogenesis.