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GDNF family receptor alpha 2 promotes neuroblastoma cell proliferation by interacting with PTEN

Li, Zuoqing, Xie, Juntao, Fei, Yingchun, Gao, Pengfei, Xie, Qigen, Gao, Wenzong, Xu, Zhe
Biochemical and biophysical research communications 2019 v.510 no.3 pp. 339-344
animal tissues, cell proliferation, childhood, enzyme activity, luciferase, neoplasms, phosphatidylinositol 3-kinase, prognosis, protein-serine-threonine kinases, transcription (genetics)
Neuroblastoma is a childhood tumor, and high-stage neuroblastoma has a poor prognosis. The regulatory mechanisms for neuroblastoma progression are poorly understood. In present study, we found that GDNF family receptor alpha 2 (GFRA2) was upregulated in neuroblastoma cells and tissues, and its overexpression promoted neuroblastoma cell proliferation, as revealed using colony formation, soft agar growth, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays Tumor suppressor phosphatase and tensin homolog (PTEN) is an inhibitor of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) pathway that interacts with GFRA2. A luciferase activity assay showed GFRA2 inhibits the transcriptional activity of the forkhead box O (FOXO) family proteins, which suggested that GFRA2 activated the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway in GFRA2 overexpressing cells decreased cell proliferation, confirming that GFRA2 promoted neuroblastoma cell proliferation by activating the PI3K/AKT pathway. In summary, cell proliferation via the GFRA2-PTEN-PI3K/AKT axis may represent new target to develop treatments for neuroblastoma.