Fig. 1

Schematically outlines the reported metabolic background of HNF-1α regulatory mechanism networks in various types of liver malignancies. Blockade of glucose energy metabolism by HNF-1α-driven signaling at different steps shunts the required energy that results in initiation of anti-proliferative mechanisms. On the other hand, HNF-1α also affects lipid metabolism by activating PCSK9 and inhibiting L-FABP. PCSK9 eventually leads to lysosomal degradation resulting in activation of anti-proliferative mechanisms. In the sidelines of metabolic repercussion, TNF-α blocks HNF-1α signaling which removes the NF-ƙβ signaling blockade, ultimately giving rise to malignant manifestations in the liver. Independently, HNF-1α activates HNF1A-AS1/SHP-1 signaling that has an alleviating effect on different liver malignancies. Similarly, MIA-2 is activated by HNF-1α that has showed to curtail tumorigenesis in different hepatic cancer models. A relatively well-known pro-tumorigenic cadherin-17 is documented to be blocked by HNF-1α that activates Wnt signaling, resulting in anti-carcinogenic effects within liver. SIRT is an intracellular metabolic regulator, whose deficiency is reported to inhibit HNF-1α eventually leading to carcinogenic signaling