Autotaxin表达调控机制及其生物学功能

Expression regulation mechanisms and biological functions of Autotaxin

Autotaxin(ATX)是催化溶血磷脂酸(lysophosphatidic acid,LPA)生成的关键酶,LPA可以与细胞膜上至少6种G蛋白偶联受体(称为LPA受体1-6)结合,激活各种信号转导通路,在多种生理和病理过程中发挥重要作用.ATX的表达在转录、转录后及分泌过程中受到多水平的调控,近期的研究还发现了ATX表达的表观遗传调控机制.肿瘤微环境中ATX和LPA可以促进肿瘤细胞的增殖和迁移,因此ATX-LPA通路被认为是一种潜在的癌症治疗靶点.目前,人们已经研发了多种ATX抑制剂,并发现具有临床应用潜力.本文重点关注ATX的表达调控机制和生物学功能,阐释ATX-LPA信号轴调控的生理和病理意义.

Autotaxin(ATX)is a key enzyme to produce lysophosphatidic acid(LPA).LPA interacts with at least six specific G protein-coupled receptors on cell membrane,named LPA receptor 1-6,to activate various signal pathways,and plays important roles in physiological and pathological processes.The expression of ATX is regulated at multiple levels in the process of transcription,post-transcription and secretion,and the epigenetic regulation of ATX expression has been clarified recently.ATX and LPA in the tumor microenvironment promote cell proliferation and migration,therefore ATX-LPA signaling pathway is regarded as a potential cancer therapeutic target.Several ATX inhibitors have been developed with clinical application potential.In this review,we will focus on the expression regulation mechanisms and biological functions of ATX,and demonstrate the physiological and pathological significance of ATX-LPA signaling axis.