Disruption of Tumor Suppressors HNF4 alpha/HNF1 alpha Causes Tumorigenesis in Liver

Simple SummaryLiver cancer is one of the deadliest human cancers. High-throughput analysis of cancer cell genomes has established that hotspot mutations in HNF4 alpha and HNF1 alpha occur in a variety of human cancers, including liver cancer. Here, we review recent findings pertaining to role of HNF1 alpha and HNF4 alpha in liver cancer, and their possible targeting for liver cancer treatment.The hepatocyte nuclear factor-4 alpha (HNF4 alpha) and hepatocyte nuclear factor-1 alpha (HNF1 alpha) are transcription factors that influence the development and maintenance of homeostasis in a variety of tissues, including the liver. As such, disruptions in their transcriptional networks can herald a number of pathologies, such as tumorigenesis. Largely considered tumor suppressants in liver cancer, these transcription factors regulate key events of inflammation, epithelial-mesenchymal transition, metabolic reprogramming, and the differentiation status of the cell. High-throughput analysis of cancer cell genomes has identified a number of hotspot mutations in HNF1 alpha and HNF4 alpha in liver cancer. Such results also showcase HNF1 alpha and HNF4 alpha as important therapeutic targets helping us step into the era of personalized medicine. In this review, we update current findings on the roles of HNF1 alpha and HNF4 alpha in liver cancer development and progression. It covers the molecular mechanisms of HNF1 alpha and HNF4 alpha dysregulation and also highlights the potential of HNF4 alpha as a therapeutic target in liver cancer.