The impact of hepatocyte nuclear factor-1α on liver malignancies and cell stemness with metabolic consequences

Hepatocyte nuclear factor-1 alpha (HNF-1α) is a transcription factor expressed predominantly in the liver among other organs. Structurally, it contains POU-homeodomain that binds to DNA and form proteins that help in maintaining cellular homeostasis, controlling metabolism, and differentiating cell lineages. Scientific research over the period of three decades has reported it as an important player in various liver malignancies such as hepatocellular cancers (HCCs), hepatocellular adenoma (HA), and a more specific HNF-1α-inactivated human hepatocellular adenoma (H-HCAs). Abundant clinical and rodent data have noted the downregulation of HNF-1α in parallel with liver malignancies. It is also interesting to notice that the co-occurrence of mutated HNF-1α expression and hepatic carcinomas transpires typically along with metabolic repercussion. Moreover, scientific data implies that HNF-1α exerts its effects on cell stemness and hence can indirectly impact liver malignancies and metabolic functioning. The effects of HNF-1α on cell stemness present a future opportunity to explore a possible and potential breakthrough. Although the mechanism through which inactivated HNF-1α leads to hepatic malignancies remain largely obscure, several key signal molecules or pathways, including TNF-α, SHP-1, CDH17, SIRT, and MIA-2, have been reported to take part in the regulations of HNF-1α. It can be concluded from the present scientific data that HNF-1α has a great potential to serve as a target for liver malignancies and cell stemness.