Autotaxin(ATX)具有LysoPLD活性，催化溶血磷脂酰胆碱(LPC)水解生成溶血磷脂酸(LPA)。LPA作用于细胞膜上的LPA受体，参与血管生成、炎症反应和肿瘤发生等多种生理和病理过程。ATX在一些肿瘤细胞中的高表达，ATX-LPA信号通路促进肿瘤细胞的生存、迁移和侵润，被认为是肿瘤治疗的靶点，但是在另外一些肿瘤细胞中ATX则表达水平极低或不表达。我们的前期研究发现，表观遗传机制在肿瘤细胞ATX表达调控中发挥重要作用，PRC2介导的组蛋白H3K27me3修饰是抑制ATX表达的关键因素。在CoCl2处理或缺氧条件下，ATX启动子区域的H3K27me3水平降低，H3K27ac水平升高，导致这些肿瘤细胞中原本沉默的ATX基因被诱导表达。在本项目中我们将深入阐明肿瘤细胞ATX表达调控的表观遗传机制，揭示ATX-LPA通路参与肿瘤细胞缺氧应激的机理及其在肿瘤发生发展中的作用。

Autotaxin is a secreted glycoprotein with lysophospholipase D (LysoPLD) activity, catalyzing the hydrolysis of lysophosphatidylcholine (LPC) to generate lysophosphatidic acid (LPA). LPA, through interacting with the LPA receptors on cellular membrane, takes parts in a variety of human physiological and pathological processes, such as angiogenesis, inflammation, and oncogenesis. ATX is highly expressed in several type of cancer cells, and promotes the survival, migration and invasion of cancer cell through the ATX-LPA axis, which is regarded as a critical target for cancer therapy. However, in some other cancer cells ATX expression level is very low or undetectable. In our previous study, we have found that epigenetic mechanism plays a key role in ATX expression regulation. It was found that ATX expression was suppressed by PRC2-mediated H3K27me3 modification. Under the CoCl2 treatment or hypoxic condition, the suppressed ATX expression in cancer cells was significantly activated, with the decrease of H3K27me3 level and the increase of H3K27Ac level in ATX promoter region. In this project, we will clarify epigenetic mechanism of ATX expression regulation in cancer cells, elucidate the effects and mechanism of ATX-LPA axis in hypoxic stress response, and explore the role of ATX-LPA axis in oncogenesis and cancer progression.