Department of Toxicology, Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo), Dortmund, Germany.
Interface Processes, Leibniz Institut für Analytische Wissenschaften - ISAS e.V., Dortmund, Germany.
Cancer Res. 2017 Sep 1;77(17):4589-4601. doi: 10.1158/0008-5472.CAN-16-2065. Epub 2017 Jun 26.
Glycerophosphodiesterase EDI3 (GPCPD1; GDE5; GDPD6) has been suggested to promote cell migration, adhesion, and spreading, but its mechanisms of action remain uncertain. In this study, we targeted the glycerol-3-phosphate acyltransferase GPAM along with choline kinase-α (CHKA), the enzymes that catabolize the products of EDI3 to determine which downstream pathway is relevant for migration. Our results clearly showed that GPAM influenced cell migration via the signaling lipid lysophosphatidic acid (LPA), linking it with GPAM to cell migration. Analysis of GPAM expression in different cancer types revealed a significant association between high GPAM expression and reduced overall survival in ovarian cancer. Silencing GPAM in ovarian cancer cells decreased cell migration and reduced the growth of tumor xenografts. In contrast to these observations, manipulating CHKA did not influence cell migration in the same set of cell lines. Overall, our findings show how GPAM influences intracellular LPA levels to promote cell migration and tumor growth. .
甘油磷酸二酯酶 EDI3（GPCPD1；GDE5；GDPD6）被认为可以促进细胞迁移、黏附和铺展，但它的作用机制仍不确定。在这项研究中，我们针对甘油-3-磷酸酰基转移酶 GPAM 以及胆碱激酶-α（CHKA），即代谢 EDI3 产物的酶，以确定哪个下游途径与迁移相关。我们的结果清楚地表明，GPAM 通过信号脂质溶血磷脂酸（LPA）影响细胞迁移，将其与 GPAM 与细胞迁移联系起来。对不同癌症类型中 GPAM 表达的分析表明，卵巢癌中高 GPAM 表达与总生存率降低之间存在显著关联。在卵巢癌细胞中沉默 GPAM 会降低细胞迁移并减少肿瘤异种移植物的生长。与这些观察结果相反，在相同的细胞系中操纵 CHKA 并不影响细胞迁移。总的来说，我们的研究结果表明 GPAM 如何影响细胞内 LPA 水平以促进细胞迁移和肿瘤生长。
