Department of Pharmacology, Tokyo Women's Medical University, Shinjuku, Tokyo, Japan.
Cancer Sci. 2019 Mar;110(3):841-848. doi: 10.1111/cas.13942. Epub 2019 Feb 15.
The biological functions of the Eph/ephrin system have been intensively investigated and well documented so far since its discovery in 1987. Although the Eph/ephrin system has been implicated in pathological settings such as Alzheimer's disease and cancer, the molecular mechanism of the Eph/ephrin system in those diseases is not well understood. Especially in cancer, recent studies have demonstrated that most of Eph and ephrin are up- or down-regulated in various types of cancer, and have been implicated in tumor progression, tumor malignancy, and prognosis. However, they lack consistency and are in controversy. The localization patterns of EphA1 and EphA2 in mouse lungs are very similar, and both knockout mice showed similar phenotypes in the lungs. Ephrin-A1 that is a membrane-anchored ligand for EphAs was co-localized with EphA1 and EphA2 in lung vascular endothelial cells. We recently uncovered the molecular mechanism of ephrin-A1-induced lung metastasis by understanding the physiological function of ephrin-A1 in lungs. This review focuses on the function of EphA1, EphA2, and ephrin-A1 in tumors and an establishment of pre-metastatic microenvironment in the lungs.
Eph/ephrin 系统的生物学功能自 1987 年发现以来，已经得到了深入的研究和充分的证实。尽管 Eph/ephrin 系统已被牵涉到阿尔茨海默病和癌症等病理环境中，但该系统在这些疾病中的分子机制尚不清楚。特别是在癌症中，最近的研究表明，大多数 Eph 和 ephrin 在各种类型的癌症中上调或下调，并且与肿瘤进展、肿瘤恶性程度和预后有关。然而，它们缺乏一致性，存在争议。EphA1 和 EphA2 在小鼠肺部的定位模式非常相似，两种敲除小鼠在肺部表现出相似的表型。Ephrin-A1 是 EphAs 的膜锚定配体，与 EphA1 和 EphA2 在肺血管内皮细胞中共定位。我们最近通过了解 Ephrin-A1 在肺部的生理功能，揭示了 Ephrin-A1 诱导肺转移的分子机制。这篇综述重点介绍了 EphA1、EphA2 和 Ephrin-A1 在肿瘤中的作用以及在肺部建立前转移微环境的作用。
