Leukemia inhibitory factor receptor (LIFR) (LIFR)

Leukemia inhibitory factor receptor (LIFR) is a transmembrane protein that belongs to the type I cytokine receptor family and serves as a critical component of the signaling machinery for several IL-6 family cytokines (UniProt: P42702). Upon binding its primary ligand, Leukemia Inhibitory Factor (LIF), LIFR heterodimerizes with the glycoprotein 130 (gp130) subunit to initiate intracellular cascades, most notably the JAK/STAT3, MAPK, and PI3K pathways (NCBI Gene: 3977). These pathways are essential for diverse biological processes, including embryonic stem cell self-renewal, bone remodeling, and neuronal development. In the context of human disease, LIFR has a complex role; it is frequently downregulated in certain cancers where it acts as a metastasis suppressor, yet it is upregulated in others to promote chemoresistance and cancer stem cell maintenance (PubMed: 22901811). Genetic loss-of-function mutations in LIFR are the primary cause of Stüve-Wiedemann syndrome, a rare and severe autosomal recessive disorder characterized by skeletal deformities and dysautonomia (OMIM: 601559). Current pharmacological interest focuses on modulating the LIF/LIFR axis, with small molecule inhibitors like EC359 being developed to disrupt the receptor's interaction with its ligands in solid tumors (PubMed: 31113817). Monitoring LIFR expression and downstream STAT3 activation serves as a potential strategy for patient stratification in clinical trials targeting this pathway.

Other names

Leukemia inhibitory factor receptor alphaLIF receptor alphaCD118SWSSTWSLIF-R

Small molecule antagonism of the LIFR extracellular domain to prevent ligand binding and subsequent gp130-mediated signal transduction (PubMed: 31113817).