Yan Meng, Zhao Ronglan, Xue Yanwen, Cao Yahui, Du Yanan, Peng Xiaoxiang
School of Medical Laboratory, Shandong Second Medical University, Weifang, Shandong, China.
Shandong Advanced Academy Engineering Research Institute of Precision Medicine Innovation and Transformation of Infections Diseases, Shandong Second Medical University, Weifang, Shandong, China.
J Neurosci Res. 2025 Jul;103(7):e70065. doi: 10.1002/jnr.70065.
Glioma is the most common primary brain tumor, characterized by high invasiveness and poor prognosis. The purinergic ligand-gated ion channel 7 receptor (P2X7R), an ion channel-type purinergic receptor with adenosine triphosphate (ATP) as its ligand, is widely expressed in various tumor cells, including glioma. Moreover, it plays crucial biological functions in the progression of glioma. P2X7R promotes the proliferation, invasion, and metastasis of glioma by activating multiple signaling pathways, facilitating epithelial-mesenchymal transition (EMT), promoting the release of extracellular vesicles (EVs) and regulating the tumor microenvironment (TME) of glioma. However, the activation of P2X7R by high concentrations of ATP can induce cell necrosis or pyroptosis, exerting an anti-glioma effect. The bidirectional nature of its functions may be related to differences in the subtypes of P2X7R, cell types, as well as the TME. P2X7R antagonists can inhibit its effect in glioma, while the expression of P2X7R can enhance the efficacy of radiotherapy and chemotherapy. In this review, the structure and function of P2X7R, its role in tumor, especially its mechanism of action in glioma, and its latent capacity value as a target for therapeutic of glioma were reviewed in detail.
胶质瘤是最常见的原发性脑肿瘤,具有高侵袭性和预后差的特点。嘌呤能配体门控离子通道7受体(P2X7R)是一种以三磷酸腺苷(ATP)为配体的离子通道型嘌呤能受体,广泛表达于包括胶质瘤在内的各种肿瘤细胞中。此外,它在胶质瘤的进展中发挥着关键的生物学功能。P2X7R通过激活多种信号通路、促进上皮-间质转化(EMT)、促进细胞外囊泡(EVs)释放以及调节胶质瘤的肿瘤微环境(TME)来促进胶质瘤的增殖、侵袭和转移。然而,高浓度ATP激活P2X7R可诱导细胞坏死或焦亡,发挥抗胶质瘤作用。其功能的双向性可能与P2X7R亚型、细胞类型以及TME的差异有关。P2X7R拮抗剂可抑制其在胶质瘤中的作用,而P2X7R的表达可增强放疗和化疗的疗效。在本综述中,详细阐述了P2X7R的结构与功能、其在肿瘤中的作用,尤其是在胶质瘤中的作用机制,以及其作为胶质瘤治疗靶点的潜在价值。