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从青蛙视角看EphrinB信号传导。

A frog's view of EphrinB signaling.

作者信息

Hwang Yoo-Seok, Daar Ira O

机构信息

Cancer and Developmental Biology Laboratory, National Cancer Institute, Frederick, Maryland, 21702.

出版信息

Genesis. 2017 Jan;55(1-2). doi: 10.1002/dvg.23002.

Abstract

Cell-cell and cell-substrate adhesion are essential to the proper formation and maintenance of tissue patterns during development, and deregulation of these processes can lead to invasion and metastasis of cancer cells. Cell surface adhesion and signaling molecules are key players in both normal development and cancer progression. One set of cell surface proteins, the Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, are significant regulators of these processes. During embryonic development, the Eph/ephrin signaling system is involved in cell-cell contact events that result in cell sorting and boundary formation between receptor and ligand bearing cells. When migrating cells that display the membrane bound ligands or receptors come in contact with cells bearing the cognate partner, the response may be adhesion or repulsion, ultimately leading to the proper positioning of these cells. During cancer progression, the signaling between these receptor/ligand pairs is often deregulated, leading to increased invasion and metastasis. To gain mechanistic insight into the pathways that mediate Eph receptor and ephrin signaling we have relied upon a very tractable system, the frog Xenopus. This model system has proven to be extremely versatile, and represents a relatively quick and manipulable system to explore signaling events and the in vivo processes affected by these signals.

摘要

细胞间和细胞与底物的黏附对于发育过程中组织模式的正确形成和维持至关重要,而这些过程的失调会导致癌细胞的侵袭和转移。细胞表面黏附分子和信号分子在正常发育和癌症进展中均起着关键作用。一组细胞表面蛋白,即Eph受体酪氨酸激酶及其膜结合配体—— Ephrin,是这些过程的重要调节因子。在胚胎发育过程中,Eph/Ephrin信号系统参与细胞间接触事件,这些事件导致细胞分选以及表达受体和配体的细胞之间形成边界。当表达膜结合配体或受体的迁移细胞与携带同源伴侣的细胞接触时,反应可能是黏附或排斥,最终导致这些细胞的正确定位。在癌症进展过程中,这些受体/配体对之间的信号传导常常失调,导致侵袭和转移增加。为了深入了解介导Eph受体和Ephrin信号传导的途径,我们依赖于一个非常易于处理的系统——非洲爪蟾。这个模型系统已被证明具有极强的通用性,是一个相对快速且易于操作的系统,可用于探索信号传导事件以及受这些信号影响的体内过程。

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