P2X7R: A Critical Regulator and Potential Therapeutic Target for Glioma

IF 2.9 3区医学 Q2 NEUROSCIENCES

Journal of Neuroscience Research Pub Date : 2025-07-03 DOI:10.1002/jnr.70065

Meng Yan, Ronglan Zhao, Yanwen Xue, Yahui Cao, Yanan Du, Xiaoxiang Peng

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Abstract

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.

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P2X7R：神经胶质瘤的关键调控因子和潜在治疗靶点

胶质瘤是最常见的原发性脑肿瘤，具有侵袭性高、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，在包括胶质瘤在内的多种肿瘤细胞中广泛表达。此外，它在胶质瘤的发展中起着至关重要的生物学作用。P2X7R通过激活多种信号通路，促进上皮-间质转化（epithelial-mesenchymal transition， EMT），促进细胞外囊泡（extracellular vesicles, EVs）的释放，调节胶质瘤的肿瘤微环境（tumor microenvironment， TME），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。本文就P2X7R的结构和功能、在肿瘤中的作用，特别是在胶质瘤中的作用机制，以及作为胶质瘤治疗靶点的潜在容量价值等方面进行了综述。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Neuroscience Research 医学-神经科学

CiteScore

9.50

自引率

2.40%

发文量

145

审稿时长

1 months

期刊介绍： The Journal of Neuroscience Research (JNR) publishes novel research results that will advance our understanding of the development, function and pathophysiology of the nervous system, using molecular, cellular, systems, and translational approaches. JNR covers both basic research and clinical aspects of neurology, neuropathology, psychiatry or psychology. The journal focuses on uncovering the intricacies of brain structure and function. Research published in JNR covers all species from invertebrates to humans, and the reports inform the readers about the function and organization of the nervous system, with emphasis on how disease modifies the function and organization.