The Glycosylphosphatidylinositol-linked Glial Cell Derived Neurotrophic Factor (GDNF) receptor alpha (GFRA) is a coreceptor that recognizes the GDNF family of ligands and plays a crucial role in the development and maintenance of the nervous system. Among the four identified GFRA isoforms, GFRA1 specifically binds to GDNF and is involved in the regulation of neuronal cell proliferation, differentiation, and migration. Additionally, GFRA1 has been implicated in cancer cell progression and metastasis.
Recent research indicates that GFRA1 can contribute to the development of chemoresistance in osteosarcoma. GFRA1 expression is induced following treatment of osteosarcoma cells with the widely used anticancer drug, cisplatin. This induction of GFRA1 expression significantly suppresses apoptosis mediated by cisplatin in osteosarcoma cells. Furthermore, GFRA1 expression promotes autophagy by activating the SRC-AMPK signaling axis after cisplatin treatment, leading to enhanced survival of osteosarcoma cells.
GFRA1-induced autophagy has been shown to promote tumor growth in mouse xenograft models, suggesting a novel function for GFRA1 in osteosarcoma chemoresistance.