文章：

癌症中的Eph受体和ephrins：双向信号传导及其他

Eph receptors and ephrins in cancer: bidirectional signalling and beyond

原文发布日期：2010-03-01

DOI: 10.1038/nrc2806

类型: Review Article

开放获取: 否

要点：

1. The Eph receptors are the largest family of receptor tyrosine kinases. They bind glycosylphosphatidylinositol (GPI)-linked and transmembrane ephrin ligands, generating bidirectional signals at sites of cell–cell contact.
2. Eph receptors and/or ephrins are widely expressed in cancer cells and tumour stroma, but they can be downregulated at advanced cancer stages. Often Eph receptor and ephrin levels are discordantly regulated. In addition to changes in expression levels, Eph receptor mutations are also likely to have a role in cancer pathogenesis.
3. In many cellular contexts, Eph bidirectional signalling promotes an epithelial phenotype and suppresses cancer cell–substrate adhesion, migration, invasion and growth. Consistent with this, Eph receptor signalling seems to be low in many cancer cells owing to an imbalance of Eph and ephrin expression or the inability of receptor and ligand to interact effectively.
4. Eph receptors and ephrins can also promote cancer progression through poorly understood mechanisms that do not involve reciprocal association but rather depend on crosstalk with oncogenic signalling pathways. In addition, Eph bidirectional signals promote tumour angiogenesis.
5. Eph receptors and ephrins are promising new therapeutic targets in cancer, and many Eph-based approaches show promise for prognosis and therapy.

要点翻译：

1. Eph受体是最大的受体酪氨酸激酶家族。它们与糖基磷脂酰肌醇（GPI）锚定蛋白和跨膜ephrin配体结合，在细胞-细胞接触部位产生双向信号。
2. Eph受体和/或ephrin在癌细胞和肿瘤基质中广泛表达，但在晚期癌症阶段可能下调。通常Eph受体与ephrin的表达水平呈现不一致的调控。除表达水平变化外，Eph受体突变也可能在癌症发病机制中发挥作用。
3. 在多种细胞环境中，Eph双向信号传导可促进上皮表型，并抑制癌细胞-基质粘附、迁移、侵袭和生长。与此一致的是，由于Eph与ephrin表达失衡或受体与配体无法有效相互作用，许多癌细胞中的Eph受体信号传导往往较弱。
4. Eph受体和ephrin还能通过机制不明的非互作依赖性方式促进癌症进展，这类机制主要依赖于与致癌信号通路的串扰。此外，Eph双向信号可促进肿瘤血管生成。
5. Eph受体和ephrin是极具前景的癌症治疗新靶点，许多基于Eph的研究方法在预后判断和治疗方面展现出潜力。

英文摘要：

The Eph receptor tyrosine kinases and their ephrin ligands have intriguing expression patterns in cancer cells and tumour blood vessels, which suggest important roles for their bidirectional signals in many aspects of cancer development and progression. Eph gene mutations probably also contribute to cancer pathogenesis. Eph receptors and ephrins have been shown to affect the growth, migration and invasion of cancer cells in culture as well as tumour growth, invasiveness, angiogenesis and metastasis in vivo. However, Eph signalling activities in cancer seem to be complex, and are characterized by puzzling dichotomies. Nevertheless, the Eph receptors are promising new therapeutic targets in cancer.

摘要翻译： 

Eph受体酪氨酸激酶及其ephrin配体在癌细胞和肿瘤血管中表现出独特的表达模式，提示其双向信号在癌症发生发展的多个环节中可能发挥重要作用。Eph基因突变很可能也参与了癌症的致病过程。已有研究表明，Eph受体和ephrins可在体外影响癌细胞的增殖、迁移与侵袭，并在体内调控肿瘤的生长、侵袭性、血管生成及转移。然而，Eph信号在癌症中的作用似乎十分复杂，常表现出令人困惑的双重特性。尽管如此，Eph受体仍是癌症治疗中极具前景的新靶点。

原文链接：

Eph receptors and ephrins in cancer: bidirectional signalling and beyond