Department of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, AL 35205, USA.
FEBS Lett. 2012 Jul 30;586(16):2360-5. doi: 10.1016/j.febslet.2012.05.047. Epub 2012 Jun 5.
Serotonin, a known neurotransmitter, also functions as an angiokine to promote angiogenesis. The majority of serotonin in the human body is stored in platelets, and platelet aggregation leads to significant release of serotonin in thrombotic tumor environment. We have investigated serotonin signaling in human endothelial cells. Through G-protein-coupled receptors, serotonin at physiologically relevant concentrations activated Src/PI3K/AKT/mTOR/p70S6K phosphorylation signaling, and this activation was similar to that seen with VEGF. This finding provides insight into the overlapping angiogenic signaling pathways stimulated by serotonin in tumor environment, and suggests one of the mechanisms underlying resistance to current VEGF-targeting antiangiogenic therapy against cancer.
血清素是一种已知的神经递质，也作为血管生成素发挥作用，促进血管生成。人体内的大多数血清素储存在血小板中，血小板聚集会导致血栓性肿瘤环境中血清素的大量释放。我们已经研究了人类内皮细胞中的血清素信号转导。通过 G 蛋白偶联受体，生理相关浓度的血清素激活了Src/PI3K/AKT/mTOR/p70S6K 磷酸化信号转导，这种激活与 VEGF 相似。这一发现深入了解了在肿瘤环境中由血清素刺激的重叠血管生成信号通路，并提示了目前针对癌症的 VEGF 靶向抗血管生成治疗产生耐药性的机制之一。
