Pegoraro Anna, De Marchi Elena, Adinolfi Elena
Department of Medical Sciences, Section of Experimental Medicine, University of Ferrara, Via Luigi Borsari 46, 44121 Ferrara, Italy.
Cells. 2021 Jan 19;10(1):189. doi: 10.3390/cells10010189.
The P2X7 receptor for extracellular ATP is a well-established mediator of tumoral development and progression both in solid cancers and hematological malignancies. The human P2X7 gene is highly polymorphic, and several splice variants of the receptor have been identified in time. P2X7 single-nucleotide polymorphisms (SNPs) have been broadly analyzed by studies relating them to pathologies as different as infectious, inflammatory, nervous, and bone diseases, among which cancer is included. Moreover, in the last years, an increasing number of reports concentrated on P2X7 splice variants' different roles and their implications in pathological conditions, including oncogenesis. Here, we give an overview of established and recent literature demonstrating a role for human P2X7 gene products in oncological conditions, mainly focusing on current data emerging on P2X7 isoform B and nfP2X7. We explored the role of these and other genetic variants of P2X7 in cancer insurgence, dissemination, and progression, as well as the effect of chemotherapy on isoforms expression. The described literature strongly suggests that P2X7 variants are potential new biomarkers and therapeutical targets in oncological conditions and that their study in carcinogenesis deserves to be further pursued.
细胞外ATP的P2X7受体是实体癌和血液系统恶性肿瘤中肿瘤发生和进展的公认介质。人类P2X7基因具有高度多态性,并且随着时间的推移已鉴定出该受体的几种剪接变体。P2X7单核苷酸多态性(SNP)已通过将它们与诸如感染性、炎症性、神经性和骨疾病等不同的病理学相关的研究进行了广泛分析,其中包括癌症。此外,在过去几年中,越来越多的报告集中在P2X7剪接变体的不同作用及其在包括肿瘤发生在内的病理状况中的影响。在这里,我们概述了已发表的和最近的文献,这些文献证明了人类P2X7基因产物在肿瘤状况中的作用,主要关注P2X7同工型B和nfP2X7出现的当前数据。我们探讨了P2X7的这些和其他基因变体在癌症发生、扩散和进展中的作用,以及化疗对同工型表达的影响。所述文献强烈表明,P2X7变体是肿瘤状况中潜在的新生物标志物和治疗靶点,并且它们在致癌作用中的研究值得进一步深入。