文章：

靶向肿瘤坏死因子超家族的死亡和诱饵受体

Targeting death and decoy receptors of the tumour-necrosis factor superfamily

原文发布日期：2002-06-01

DOI: 10.1038/nrc821

类型: Review Article

开放获取: 否

要点：

1. Tumour-necrosis factor (TNF) was discovered many years ago as a serum factor that was able to kill cancer cells in mice. The TNF receptor (TNFR) was shown to be expressed by mammalian cells years later, and led to the discovery of a superfamily of transmembrane proteins. These discoveries led to the identification of two gene families that include 18 ligands and 28 receptors, many of which are being targeted as anticancer therapies.
2. TNFR signalling was discovered to be an important aspect of the immune response, and family members such as FASL and APO2L/TRAIL induce apoptosis through a p53-independent mechanism. The signalling members of the TNFR superfamily can be divided into two main subgroups on the basis of their cytoplasmic region. One class of receptors, called death receptors (DR), contains a cytoplasmic death domain, whereas the other class does not.
3. APO2L/TRAIL has been shown to induce apoptosis in a wide variety of cancer cells, whereas most normal human cell types are resistant to APO2L/TRAIL-induced cell death.
4. Some TNFR family members do not signal, but act as 'decoys' that compete with receptors for ligands. A number of tumour types overexpress decoy receptors.
5. Treatment with factors that activate death-receptor signalling on cancer cells, and antibodies or small molecules that antagonize decoy receptors, might be an effective anticancer strategy.

要点翻译：

1. 肿瘤坏死因子（TNF）多年前被发现时，是一种能够杀死小鼠癌细胞的血清因子。数年后研究发现哺乳动物细胞可表达肿瘤坏死因子受体（TNFR），该发现引领了一个跨膜蛋白超家族的发现。这些突破促使两个基因家族得以鉴定，共包含18种配体和28种受体，其中许多已成为抗癌治疗的靶点。
2. TNFR信号通路被发现是免疫应答的重要环节，FASL和APO2L/TRAIL等家族成员通过p53非依赖机制诱导细胞凋亡。根据胞质区结构特征，TNFR超家族信号成员可分为两大亚群：一类被称为死亡受体（DR），其胞质区含有死亡结构域；另一类则不含该结构域。
3. APO2L/TRAIL已被证实可诱导多种癌细胞凋亡，而大多数正常人体细胞类型对APO2L/TRAIL诱导的细胞死亡具有抗性。
4. 部分TNFR家族成员不参与信号传导，而是作为"诱饵受体"与功能性受体竞争配体。多种肿瘤类型会过度表达这类诱饵受体。
5. 通过激活癌细胞死亡受体信号通路的因子，以及拮抗诱饵受体的抗体或小分子进行治疗，可能成为有效的抗癌策略。

英文摘要：

Cancer cells often develop resistance to chemotherapy or irradiation through mutations in the p53 tumour-suppressor gene, which prevent apoptosis induction in response to cellular damage. Death receptors — members of the tumour-necrosis factor receptor (TNFR) superfamily — signal apoptosis independently of p53. Decoy receptors, by contrast, are a non-signalling subset of the TNFR superfamily that attenuate death-receptor function. Agents that are designed to activate death receptors (or block decoy receptors) might therefore be used to kill tumour cells that are resistant to conventional cancer therapies.

摘要翻译： 

癌细胞常通过p53抑癌基因突变对化疗或放疗产生耐药性，从而阻止细胞损伤后诱导凋亡。死亡受体——肿瘤坏死因子受体（TNFR）超家族成员——可不依赖p53信号诱导凋亡。相反，诱饵受体是TNFR超家族中无信号传导功能的一类，可削弱死亡受体功能。因此，设计用于激活死亡受体（或阻断诱饵受体）的药物，有望杀伤对传统癌症治疗耐药的肿瘤细胞。

原文链接：

Targeting death and decoy receptors of the tumour-necrosis factor superfamily