Hrg, or histidine-rich glycoprotein, is a protein-encoding gene with diverse functions. It plays roles in multiple biological processes, including the regulation of blood coagulation, clearance of apoptotic cells, and tumor growth. It binds to various factors and is involved in pathways such as the PI3K and NF-κB pathways [3].

In liver cancer, Hepatocellular carcinoma cells reduce Hrg secretion, which in turn promotes neutrophil recruitment and the formation of neutrophil extracellular traps (NETs), thus facilitating lung metastasis. Hrg binds to FCγR1 on neutrophils, inhibiting PI3K and NF-κB activation to reduce IL-8 secretion and neutrophil recruitment. It also inhibits IL8-MAPK and NF-κB pathway activation and ROS production, leading to decreased NETs formation [1]. In Hepatocellular Carcinoma, Hrg directly interacts with TNFR1, stabilizes TNFR1 protein, and promotes the formation of TNFR1-complex II, which switches TNFR1-mediated cell survival to apoptosis. Down-regulation of Hrg is a result of feedback inhibition of NF-κB activation in HCC [2].

In conclusion, Hrg is crucial in regulating tumor-related processes, especially in liver cancer metastasis and apoptosis regulation. The findings from these studies help understand the complex mechanisms in cancer development and suggest that Hrg could be a potential target for treating liver cancer metastasis and progression.