Federico Lorenzo, Jeong Kang Jin, Vellano Christopher P, Mills Gordon B
Department of Systems Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX
Department of Systems Biology, University of Texas M. D. Anderson Cancer Center, Houston, TX.
J Lipid Res. 2016 Jan;57(1):25-35. doi: 10.1194/jlr.R060020. Epub 2015 May 14.
The ectonucleotide pyrophosphatase/phosphodiesterase type 2, more commonly known as autotaxin (ATX), is an ecto-lysophospholipase D encoded by the human ENNP2 gene. ATX is expressed in multiple tissues and participates in numerous key physiologic and pathologic processes, including neural development, obesity, inflammation, and oncogenesis, through the generation of the bioactive lipid, lysophosphatidic acid. Overwhelming evidence indicates that altered ATX activity leads to oncogenesis and cancer progression through the modulation of multiple hallmarks of cancer pathobiology. Here, we review the structural and catalytic characteristics of the ectoenzyme, how its expression and maturation processes are regulated, and how the systemic integration of its pleomorphic effects on cells and tissues may contribute to cancer initiation, progression, and therapy. Additionally, the up-to-date spectrum of the most frequent ATX genomic alterations from The Cancer Genome Atlas project is reported for a subset of cancers.
2型胞外核苷酸焦磷酸酶/磷酸二酯酶，更常见的名称是自分泌运动因子（ATX），是一种由人类ENNP2基因编码的胞外溶血磷脂酶D。ATX在多种组织中表达，并通过生成生物活性脂质溶血磷脂酸参与众多关键的生理和病理过程，包括神经发育、肥胖、炎症和肿瘤发生。大量证据表明，ATX活性改变通过调节癌症病理生物学的多个标志导致肿瘤发生和癌症进展。在这里，我们综述了这种胞外酶的结构和催化特性、其表达和成熟过程是如何被调控的，以及其对细胞和组织的多形性效应的系统整合如何可能促进癌症的起始、进展和治疗。此外，还报告了癌症基因组图谱项目中一部分癌症最常见的ATX基因组改变的最新情况。
