Lysophosphatidic Acid Signaling in Cancer Cells: What Makes LPA So Special?
Lysophosphatidic Acid Signaling in Cancer Cells: What Makes LPA So Special?
复制标题
癌细胞中的溶血磷脂酸信号传导：是什么使LPA如此特别？
DOI：
10.3390/cells10082059
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发表时间：
2021-08-11
期刊：
影响因子：
6
通讯作者：
Meier KE
中科院分区：
文献类型：
--
作者：
Balijepalli P;Sitton CC;Meier KE
溶血磷脂酸（LPA）是指作为G蛋白偶联受体配体的简单磷脂家族。虽然LPA在正常的生理环境中在整个身体中发挥作用，但从治疗的角度来看，其在癌症中的病理作用非常有趣。许多LPA受体（LPAR）与多种G蛋白偶联，并且通常在任何给定细胞上表达多于一种LPAR。虽然单个受体通过常规GPCR途径发出信号，但LPA在刺激癌细胞增殖和迁移方面特别有效。本文综述了这些促肿瘤作用的机制方面。我们提供了各种类型癌症中LPA信号应答的例子，重点是那些已经确定了特定LPAR作用的癌症。虽然提供了LPAR信号转导的概述，这些例子也揭示了我们在受体水平上的LPA作用机制的知识差距。目前的理解LPAR的结构和LPAR与其他受体的相互作用的作用进行了讨论。总体而言，LPAR提供了对潜在分子机制的深入了解，这些潜在分子机制是单个GPCR（或GPCR的组合）从其激动剂配体引发独特反应谱的能力的基础。对这些机制的进一步了解将为药物发现提供信息，因为GPCR是有希望的癌症治疗靶点。
Lysophosphatidic acid (LPA) refers to a family of simple phospholipids that act as ligands for G protein-coupled receptors. While LPA exerts effects throughout the body in normal physiological circumstances, its pathological role in cancer is of great interest from a therapeutic viewpoint. The numerous LPA receptors (LPARs) are coupled to a variety of G proteins, and more than one LPAR is typically expressed on any given cell. While the individual receptors signal through conventional GPCR pathways, LPA is particularly efficacious in stimulating cancer cell proliferation and migration. This review addresses the mechanistic aspects underlying these pro-tumorigenic effects. We provide examples of LPA signaling responses in various types of cancers, with an emphasis on those where roles have been identified for specific LPARs. While providing an overview of LPAR signaling, these examples also reveal gaps in our knowledge regarding the mechanisms of LPA action at the receptor level. The current understanding of the LPAR structure and the roles of LPAR interactions with other receptors are discussed. Overall, LPARs provide insight into the potential molecular mechanisms that underlie the ability of individual GPCRs (or combinations of GPCRs) to elicit a unique spectrum of responses from their agonist ligands. Further knowledge of these mechanisms will inform drug discovery, since GPCRs are promising therapeutic targets for cancer.
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