Equipe labellisée par la Ligue contre le cancer, Centre de Recherche des Cordeliers, INSERM U1138, Sorbonne Université, Université de Paris, Paris, France.
Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute, Villejuif, France.
EMBO J. 2021 Jul 1;40(13):e108130. doi: 10.15252/embj.2021108130. Epub 2021 Jun 14.
While intracellular adenosine triphosphate (ATP) occupies a key position in the bioenergetic metabolism of all the cellular compartments that form the tumor microenvironment (TME), extracellular ATP operates as a potent signal transducer. The net effects of purinergic signaling on the biology of the TME depend not only on the specific receptors and cell types involved, but also on the activation status of cis- and trans-regulatory circuitries. As an additional layer of complexity, extracellular ATP is rapidly catabolized by ectonucleotidases, culminating in the accumulation of metabolites that mediate distinct biological effects. Here, we discuss the molecular and cellular mechanisms through which ATP and its degradation products influence cancer immunosurveillance, with a focus on therapeutically targetable circuitries.
虽然细胞内三磷酸腺苷(ATP)在构成肿瘤微环境(TME)的所有细胞区室的生物能量代谢中占据关键位置,但细胞外 ATP 作为一种有效的信号转导分子发挥作用。嘌呤能信号对 TME 生物学的净效应不仅取决于涉及的特定受体和细胞类型,还取决于顺式和反式调节回路的激活状态。作为一个额外的复杂层面,细胞外 ATP 被核苷酸酶迅速分解代谢,最终积累代谢产物,介导不同的生物学效应。在这里,我们讨论了 ATP 及其降解产物影响癌症免疫监视的分子和细胞机制,重点讨论了可治疗靶向的回路。