C-terminal variants of the P2X7 receptor are associated with prostate cancer progression and bone metastasis – evidence from clinical and pre-clinical data

[摘要] Bone is the most common site for metastasis in prostatecancer (PCa), and identifying clinically useful biomarkersto predict the risk of currently incurable bone metastasesis a major priority in PCa research.Extracellular adenosine triphosphate (ATP) was shownto be a major biochemical constituent of the tumormicroenvironment and regulates the tumor and host interactions by acting at P2 purinergic receptors. Among theP2 receptors, the ion channel P2X purinergic receptor 7(P2X7R) has an unusually long C-terminus containing200 amino acids, which forms the molecular basis forthe unique bi-function of P2X7R promoting cancer cellproliferation or inducing membrane permeabilization andapoptosis, upon activation by a low or high concentrationof ATP, respectively. A cysteine-rich region and a guanosine diphosphate or triphosphate (GDP/GTP)-binding sitelocated in the C-terminus are pivotal for the structuralrearrangement of the second transmembrane domain helixand the globular ballast underneath during the membranepore permeabilization [1].

[学科分类] 社会科学、人文和艺术（综合）