Regulatory mechanisms of LGR4 on cancer and cancer stem cell properties

Leucine-rich repeats containing G protein-coupled receptor 4 (LGR4) is a receptor belonging to the G-protein-coupled receptor superfamily. LGR4 can be activated by ligands such as R-spondins (RSPOs), Norrin, and the ligand of the receptor activator of nuclear factor kappa-B(RANKL) to regulate signaling pathways in both normal and pathological processes. LGR4 is widely expressed across various tissues and serves multiple functions, including organ development and maintenance, primarily regulating cell proliferation, survival, and differentiation through the Wnt/β-catenin pathway. In tumors, LGR4 is involved in the progression, invasion, and metastasis of various cancers, including colorectal, breast, prostate, lung, and skin cancers. Recent studies indicate that LGR4 plays a crucial role in regulating tumor stem cell populations by modulating their self-renewal capabilities and regulating stem cell characteristics. This review discusses the expression and functional roles of LGR4 in tumors, the molecular mechanisms regulated by LGR4, and the relationship between LGR4, tumor stem cells, and chemotherapy resistance.