Apoptosis, Cancer and Development Laboratory, Equipe labellisée La Ligue, CNRS UMR5238, Université de Lyon, Centre Léon Bérard, Lyon, France.
Curr Opin Oncol. 2010 Jan;22(1):46-54. doi: 10.1097/CCO.0b013e328333dcd1.
The dependence receptor notion has recently seen an interesting development. From a basic cell biology concept, which proposes that some transmembrane receptors can be active in the absence of their ligand and induce in the setting apoptosis, recent observations have provided new hope for the development of alternative targeted therapies. The purpose of this review is to show, with the example of netrin-1 dependence receptors, the path from cell biology to promising anticancer-targeted therapy.
The dependence receptors Deleted in Colorectal Cancer and Unc-5 homolog that bind netrin-1 had been implicated in nervous system development as they participate in neuronal navigation. They were also implicated beyond the developing brain with roles in angiogenesis regulation and homeostasis of various tissues. However, these receptors were shown to trigger apoptosis in the absence of netrin-1 and, as such, act as tumor suppressors. Recent data support the view that Deleted in Colorectal Cancer/Unc-5 homolog proapoptotic signals are indeed a safeguard mechanism regulating tumor growth and metastasis.
In this review, we will develop the different data supporting the view that a selective advantage for a tumor is to inactivate this dependence receptor's proapoptotic signal and will describe a putative therapeutic approach that is to reactivate this death signaling in tumor cells.
最近，依赖受体的概念有了有趣的发展。从一个基本的细胞生物学概念来看，一些跨膜受体在没有配体的情况下可以活跃，并在细胞凋亡的情况下诱导凋亡，最近的观察为开发替代的靶向治疗提供了新的希望。本文的目的是通过神经轴突导向因子 1 （netrin-1）依赖受体的例子，展示从细胞生物学到有前景的抗癌靶向治疗的发展路径。
与 netrin-1 结合的结直肠癌缺失基因和 Unc-5 同源物依赖受体，在神经系统发育过程中，作为神经元导航的一部分，被认为参与其中。除了发育中的大脑，它们在血管生成调节和各种组织的稳态中也发挥作用。然而，这些受体在没有 netrin-1 的情况下会引发细胞凋亡，因此作为肿瘤抑制因子发挥作用。最近的数据支持这样一种观点，即结直肠癌缺失基因/Unc-5 同源物的促凋亡信号实际上是一种调节肿瘤生长和转移的安全保障机制。
在这篇综述中，我们将讨论支持以下观点的不同数据，即肿瘤的选择性优势是使这种依赖受体的促凋亡信号失活，并将描述一种可能的治疗方法，即重新激活肿瘤细胞中的这种死亡信号。
