Effect of P2X7 receptor on tumorigenesis and its pharmacological properties

• Published in: Biomedicine & pharmacotherapy 2020-05, Vol.125, p.109844, Article 109844
• Main Authors: Zhang, Wen-jun, Hu, Ce-gui, Zhu, Zheng-ming, Luo, Hong-liang
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphate; Animals; ATP; Biomarkers; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - metabolism; Disease Susceptibility; Gene Expression Regulation, Neoplastic; Humans; Immunomodulation; Ion Channel Gating; Ligands; Neoplasms - etiology; Neoplasms - metabolism; Neoplasms - pathology; Neoplasms - therapy; P2X7R; Protein Binding; Purinergic P2X Receptor Antagonists - chemistry; Purinergic P2X Receptor Antagonists - pharmacology; Receptors, Purinergic P2X7 - chemistry; Receptors, Purinergic P2X7 - genetics; Receptors, Purinergic P2X7 - metabolism; Signal Transduction; Structure-Activity Relationship; Tumor; Tumor microenvironment; Tumor Microenvironment - genetics
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.109844

When tumors occur, tumor cells can release a large amount of ATP into the cellular stroma, resulting in high concentration of ATP in the tumor microenvironment, which binds to P2X7R on the cell surface, activates P2X7R, opens the ion channels on the cell membrane (mainly calcium influx), allows molecular substances smaller than 900 Da to enter freely, and further activates enzymes and kinases in related signaling pathways (such as JNK, AKT, ERK, PKC), thereby affecting differentiation, proliferation, apoptosis, metastasis and invasion of tumor cells. [Display omitted] •The structure and function of P2X7R gene were further summarized.•The correlation between tumor microenvironment and tumor was further elucidated.•The potential relationship between ATP and tumors was discussed.•Some data on the inhibitory effect of P2X7R antagonists on some tumors were provided.•Provided up-to-date data support for the intrinsic link between P2X7R and tumors. The occurrence and development of tumors is a multi-factor, multi-step, multi-gene pathological process, and its treatment has been the most difficult problem in the field of medicine today. Therefore, exploring the relevant factors involved in the pathogenesis of tumors, improving the diagnostic rate, treatment rate, and prognosis survival rate of tumors have become an urgent problem to be solved. A large number of studies have shown that the P2X7 receptor (P2X7R) and the tumor microenvironment play an important role in regulating the growth, apoptosis, migration and invasion of tumor cells. P2X7R is an ATP ligand-gated cationic channel receptor, which exists in most tissues of the human body. The main function of P2X7R is to regulate the relevant cells (such as macrophages, lymphocytes, and glial cells) to release damaging factors and induce apoptosis and cell death. In recent years, with continuous research and exploration of P2X7R, it has been found that P2X7R exists on the surface of most tumor cells and plays an important role in tumor pathogenesis. The activation of the P2X7R can open the ion channels on the tumor cell membrane (sodium ion, calcium ion influx and potassium ion outflow), trigger rearrangement of the cytoskeleton and changes in membrane fluidity, allow small molecule substances to enter the cell, activate enzymes and kinases in related signaling pathways in cells (such as PKA, PKC, ERK1/2, AKT, and JNK), thereby affecting the development of tumor cells, and can also indirectly affect the growth, a