文章：

溶血磷脂酸在癌症中的新作用

The emerging role of lysophosphatidic acid in cancer

原文发布日期：2003-08-01

DOI: 10.1038/nrc1143

类型: Review Article

开放获取: 否

要点：

1. Lysophosphatidic acid (LPA) is a serum phospholipid with growth-factor-like activities for many cell types. It acts through specific G-protein-coupled receptors on the cell surface.
2. LPA stimulates cell proliferation, migration and survival. In addition, LPA induces cellular shape changes, increases endothelial permeability and inhibits gap-junctional communication between adjacent cells. LPA promotes wound healing in vivo and suppresses intestinal damage following irradiation.
3. LPA receptors couple to multiple signalling pathways that are now being clarified. These pathways include those initiated by the small GTPases RAS, RHO and RAC, with RAS controlling cell-cycle progression and RHO/RAC signalling having a dominant role in (tumour) cell migration and invasion.
4. Significant levels (>1 μM) of bioactive LPA are detected in various body fluids, including serum (but not plasma), saliva, follicular fluid and malignant effusions. The mechanisms by which bioactive LPA is produced were unknown until recently.
5. Recent evidence shows that LPA is produced extracellularly from lysophosphatidylcholine by 'autotaxin' (ATX/lysoPLD). ATX/lysoPLD is a ubiquitous exo-phosphodiesterase that was originally identified as an autocrine motility factor for melanoma cells and is implicated in tumour progression. Through local production of bioactive LPA, ATX/lysoPLD might support an invasive microenvironment for tumour cells and therefore contribute to the metastatic cascade.
6. Both LPA receptors and ATX/lysoPLD are aberrantly expressed in several cancers.
7. The use of inhibitory drugs directed against LPA receptors and/or ATX/lysoPLD could be effective in suppressing tumour metastasis.

要点翻译：

1. 溶血磷脂酸（LPA）是一种具有生长因子样活性的血清磷脂，对多种细胞类型发挥作用。它通过细胞表面特定的G蛋白偶联受体介导其效应。
2. LPA能刺激细胞增殖、迁移和存活。此外，LPA可诱导细胞形态改变、增加内皮通透性并抑制相邻细胞间的缝隙连接通讯。在体内实验中，LPA能促进伤口愈合，并减轻辐射后的肠道损伤。
3. LPA受体可耦合多条目前正在被阐明的信号通路，包括由小GTP酶RAS、RHO和RAC启动的通路——其中RAS调控细胞周期进程，而RHO/RAC信号在（肿瘤）细胞迁移和侵袭过程中起主导作用。
4. 在多种体液中（包括血清、唾液、卵泡液及恶性积液等，但血浆除外）均可检测到显著水平（>1 μM）的生物活性LPA。直至近期，生物活性LPA的产生机制才得以揭示。
5. 最新研究表明，LPA是由溶血磷脂酰胆碱经"自分泌运动因子"（ATX/lysoPLD）在细胞外转化生成。ATX/lysoPLD是一种普遍存在的外切磷酸二酯酶，最初被鉴定为黑色素瘤细胞的自分泌运动因子，与肿瘤进展密切相关。通过局部产生生物活性LPA，ATX/lysoPLD可能为肿瘤细胞营造侵袭性微环境，从而促进转移级联反应。
6. LPA受体和ATX/lysoPLD在多种癌症中均存在异常表达。
7. 针对LPA受体和/或ATX/lysoPLD的抑制性药物可能有效抑制肿瘤转移。

英文摘要：

The bioactive phospholipid lysophosphatidic acid (LPA) stimulates cell proliferation, migration and survival by acting on its cognate G-protein-coupled receptors. Aberrant LPA production, receptor expression and signalling probably contribute to cancer initiation, progression and metastasis. The recent identification of ecto-enzymes that mediate the production and degradation of LPA, as well as the development of receptor-selective analogues, indicate mechanisms by which LPA production or action could be modulated for cancer therapy.

摘要翻译： 

生物活性磷脂溶血磷脂酸（LPA）通过作用于其相应的G蛋白偶联受体，刺激细胞增殖、迁移和存活。LPA的异常产生、受体表达及信号传导可能促进癌症的发生、进展和转移。近期发现的介导LPA生成与降解的外酶，以及受体选择性类似物的开发，为调控LPA的产生或作用以实现癌症治疗提供了潜在机制。

原文链接：

The emerging role of lysophosphatidic acid in cancer