与癌症相关的G 蛋白偶联受体及通路的研究进展

G蛋白偶联受体(G protein-coupled receptors,GPCRs)是一类重要的细胞膜表面跨膜蛋白受体超家族,具有7个跨膜螺旋结构。GPCRs的细胞内信号由G蛋白介导,可将激素、神经递质、药物、趋化因子等多种物理和化学的细胞外刺激穿过细胞膜转导到细胞内不同的效应分子,激活相应的信号级联系统进而影响恶性肿瘤的生长迁移过程。虽然目前药物市场上有很多治疗癌症的小分子药物属于G蛋白受体相关药物,但所作用的靶点集中于少数特定G蛋白偶联受体。因此,新的具有成药性的G蛋白偶联受体的开发具有很大的研究价值和市场潜力。本文主要以在癌症发生、发展中起重要作用的溶血磷脂酸(LPA),G蛋白偶联受体30(GPR30)、内皮素A受体(ETAR)等不同G蛋白偶联受体为分类依据,综述其与相关的信号通路在癌症进程中的作用,并对相应的小分子药物的临床应用和研究进展进行展望。

The Advancement of Pathway on G Protein-coupled Receptors(GPCRs) Target to Cancer

G protein-coupled receptors(GPCRs),also known as seven-transmembrane domain receptors,is a large protein family of transmembrane receptors that sense molecules such as hormone,neurotransmitters,drugs,chemotactic factors of physical and chemical extracellular signals outside the cell and activate inside signal transduction pathways and,ultimately,induce cellular responses including tumor growth,survival and migration.Many current drugs for cancer target to GPCRs,are directed towards only a few GPCR members.Therefore,huge efforts are currently underway to develop new GPCR-based drugs,particularly for cancer.This article reviews recent findings that present opportunities to interfere with major tumorigenic signals by manipulating GPCR-mediated pathways,such as lysophospholipids acid(LPA),G protein coupling receptor 30(GPR30) and Endothelin A subtype receptor.We also discuss current drug regarding novel GPCR targets that may provide promising opportunities for drug discovery in cancer prevention and treatment.