Hrg, or histidine-rich glycoprotein, has diverse functions. It binds to various factors and is involved in regulating processes like blood coagulation, apoptotic cell clearance, and tumor growth. It also impacts immune-related pathways, such as those related to neutrophil recruitment and activation, and can influence cell survival and apoptosis signaling [1,2,3].

In liver cancer, hepatocellular carcinoma cells reduce Hrg secretion, which in turn promotes lung metastasis by regulating neutrophil recruitment and activation, as well as neutrophil extracellular trap (NETs) formation. Hrg binds to FCγR1 on neutrophil membranes, inhibits PI3K and NF-κB activation, reduces IL-8 secretion to limit neutrophil recruitment, and inhibits IL8-MAPK and NF-κB pathway activation and ROS production to decrease NETs formation [1]. In hepatocellular carcinoma, Hrg directly interacts with TNFR1, stabilizes TNFR1 protein, promotes the formation of TNFR1-complex II, suppresses pro-survival gene expression by impairing NF-κB signaling activation, and thus switches TNFR1-mediated cell survival to apoptosis, inhibiting cell proliferation and increasing apoptosis in HCC [2].

In conclusion, Hrg is a crucial regulator involved in multiple biological processes. Studies in liver cancer and hepatocellular carcinoma models have shown its significance in metastasis and apoptosis regulation, providing potential strategies for treating related diseases. Its role in modulating immune-related pathways and cell-survival-apoptosis balance highlights its importance in understanding disease mechanisms.