P2X7 receptor is a key upstream regulator for main signaling pathways involved in neuroblastoma progression


Neuroblastoma (NB) is a neuroendocrine tumor that responsible for 15% of pediatric cancer deaths in childhood. Due to the lack of effective therapeutic strategy for advanced-stage patients, many studies aim at investigation of targets for clinical intervention against NB. Amoroso et al. demonstrated that P2X7 plays a key role in regulating the PI3K/Akt/GSK3β/MYCN and HIF1α/VEGF pathways, two main signaling pathways involved in NB progression. The article was published online in Oncogene.


P2X7, a receptor of extracellular ATP, is the best candidate responsible for tumor progression. This study showed P2X7 promotes PI3K/Akt and HIFα activation, GSK3β downregulation, VEGF secretion, and glycogen accumulation in ACN human NB cells. Two different P2X7 antagonists, AZ10606120 and A740003, can significantly suppress ACN-derived tumor progression in nude/nude mice. Furthermore, the blockade of P2X7 strongly reduced the expression level of MYCN, the best-known oncogene in NB. These findings are consistent with the overexpression of P2X7 in advanced-stage NB patients with poor prognosis. In summary, this study suggests that P2X7 receptor is an upstream mediator of PI3K/Akt/GSK3β/MYCN and HIF1α/VEGF pathways for regulating NB progression, metabolic activity and angiogenesis, indicating it may become a therapeutic target for NB treatment in the future.


Oncogene. 2015 Jan 26. doi: 10.1038/onc.2014.444.

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