Lifr, short for Leukemia inhibitory factor receptor, is a receptor that plays a significant role in multiple biological processes. It can activate oncogenic signaling pathways such as JAK/STAT3, MAPK, AKT, and mTOR when binding to leukemia inhibitory factor (LIF) [2,3]. The LIF/LIFR axis is crucial in tumor growth, progression, metastasis, stemness, and therapy resistance, and also modulates immune cell types in the tumor microenvironment [2]. Genetic models, like gene knockout mouse models, are valuable for studying Lifr's functions.

In hepatocyte-specific and inducible Lifr-knockout mice, loss of Lifr promotes liver tumorigenesis and confers resistance to drug-induced ferroptosis. Mechanistically, it activates NF-κB signaling through SHP1, upregulating the iron-sequestering cytokine LCN2, which depletes iron and renders insensitivity to ferroptosis inducers [1]. Also, loss of the liver tumor suppressor Lifr in mouse hepatocytes impairs the recruitment and activity of reparative neutrophils, inhibiting liver regeneration after partial hepatectomy or toxic injuries, while overexpression of LIFR promotes liver repair and regeneration [4].

In conclusion, Lifr plays essential roles in tumor-related processes and liver injury repair. Studies using Lifr knockout mouse models have revealed its significance in liver tumorigenesis, ferroptosis resistance, and liver regeneration. These findings contribute to understanding the underlying mechanisms of related diseases and may provide potential therapeutic targets.