The Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, Beijing 100875, China.
Cells. 2021 Apr 19;10(4):939. doi: 10.3390/cells10040939.
Autotaxin (ATX) is a secreted glycoprotein and functions as a key enzyme to produce extracellular lysophosphatidic acid (LPA). LPA interacts with at least six G protein-coupled receptors, LPAR1-6, on the cell membrane to activate various signal transduction pathways through distinct G proteins, such as Gi/0, G12/13, Gq/11, and Gs. The ATX-LPA axis plays an important role in physiological and pathological processes, including embryogenesis, obesity, and inflammation. ATX is one of the top 40 most unregulated genes in metastatic cancer, and the ATX-LPA axis is involved in the development of different types of cancers, such as colorectal cancer, ovarian cancer, breast cancer, and glioblastoma. ATX expression is under multifaceted controls at the transcription, post-transcription, and secretion levels. ATX and LPA in the tumor microenvironment not only promote cell proliferation, migration, and survival, but also increase the expression of inflammation-related circuits, which results in poor outcomes for patients with cancer. Currently, ATX is regarded as a potential cancer therapeutic target, and an increasing number of ATX inhibitors have been developed. In this review, we focus on the mechanism of ATX expression regulation and the functions of ATX in cancer development.
自分泌酶（Autotaxin，ATX）是一种分泌型糖蛋白，作为产生细胞外溶血磷脂酸（Lysophosphatidic acid，LPA）的关键酶发挥作用。LPA 通过与细胞膜上至少六种 G 蛋白偶联受体（LPAR1-6）相互作用，通过不同的 G 蛋白（如 Gi/0、G12/13、Gq/11 和 Gs）激活各种信号转导途径。ATX-LPA 轴在生理和病理过程中发挥着重要作用，包括胚胎发生、肥胖和炎症。ATX 是转移性癌症中前 40 个最不受调控的基因之一，ATX-LPA 轴参与了多种类型癌症的发展，如结直肠癌、卵巢癌、乳腺癌和神经胶质瘤。ATX 的表达在转录、转录后和分泌水平受到多方面的调控。肿瘤微环境中的 ATX 和 LPA 不仅促进细胞增殖、迁移和存活，而且增加炎症相关通路的表达，导致癌症患者的预后不良。目前，ATX 被认为是一种潜在的癌症治疗靶点，越来越多的 ATX 抑制剂被开发出来。在这篇综述中，我们重点介绍了 ATX 表达调控的机制以及 ATX 在癌症发展中的作用。
