Gfra3, known as GDNF family receptor alpha 3, is a receptor for artemin (ARTN), a glial cell line-derived neurotrophic factor (GDNF). It is involved in multiple biological processes. In early embryonic development, the artemin-Gfra3 signaling system has an autocrine/paracrine role in regulating development and apoptosis, potentially involving the MAP kinase signaling pathway [6]. In cancer, it has been associated with tumor-related processes.

In gastric cancer, high Gfra3 expression is linked to poor prognosis, and the ARTN-Gfra3 axis can induce epithelial-mesenchymal transition (EMT) phenotypes, migration, and invasion of gastric cancer cells via KRAS signaling [3]. Also, Gfra3 promoter methylation may be associated with decreased postoperative survival in gastric cancer [4]. In lung adenocarcinoma, its expression is upregulated after cuproptosis induced by elesclomol-CuCL2, and BARX1 and Gfra3 deficiency facilitates cuproptosis [2]. In hepatocellular carcinoma, Gfra3 is significantly correlated with clinical prognosis, stage, immune infiltration, response, and vital signaling pathways [5]. In neuropathic pain, Gfra3 is expressed in a spared nerve injury (SNI)-induced neuronal cluster (SNIIC1) characterized by the co-expression of Atf3 and Gal [1].

In summary, Gfra3 is crucial in embryonic development and significantly impacts various diseases, especially cancers and neuropathic pain. Studies using models related to Gfra3, such as in cancer and pain-related contexts, help uncover its role in disease-associated biological processes, providing potential targets for therapeutic interventions.