文章：

萨尔瓦多-疣-河马通路-一个新兴的肿瘤抑制网络

The Salvador–Warts–Hippo pathway — an emerging tumour-suppressor network

原文发布日期：2007-03-01

DOI: 10.1038/nrc2070

类型: Review Article

开放获取: 否

要点：

1. The Salvador–Warts–Hippo (SWH) pathway controls organ size by modulating cell growth, proliferation and apoptosis.
2. Deregulation of this pathway in Drosophila melanogaster leads to dramatic increases in organ size.
3. Proteins predicted to function in the SWH pathway include the cadherin Fat, the band 4.1 proteins Expanded and Merlin, the kinases Hippo, Warts and Discs overgrown, the adaptor molecules Salvador, Mats and Dachs, dRASSF and the transcriptional co-activator Yorkie.
4. SWH pathway components are conserved throughout evolution from yeast to humans, and the pathway has been implicated in the genesis of human cancers.
5. The human orthologue of merlin (NF2) is a bona fide tumour-suppressor gene, which is mutated in the familial cancer syndrome neurofibromatosis type 2. Homologues of warts, salvador, mats (mob as tumour suppressor), dRASSF (Ras association family) and yorkie have also been implicated in mammalian tumorigenesis.
6. Important target genes of the SWH pathway include cyclin E (which drives cell proliferation), DIAP1 (which inhibits apoptosis) and the bantam microRNA. The pathway also controls expanded and four-jointed expression in apparent regulatory feedback loops.
7. Potential regulatory processes that control SWH pathway activity include the modification of expression and sub-cellular localization of Expanded, the modulation of expression levels of Warts and the phosphorylation of Yorkie.

要点翻译：

1. 萨尔瓦多-疣-河马（SWH）通路通过调控细胞生长、增殖和凋亡来控制器官大小。
2. 在果蝇中，该通路的失调会导致器官体积显著增大。
3. 预计在SWH通路中发挥作用的蛋白质包括钙粘蛋白Fat、4.1带蛋白Expanded和Merlin、激酶Hippo、Warts和Discs overgrown、衔接分子Salvador、Mats和Dachs、dRASSF以及转录共激活因子Yorkie。
4. SWH通路组分在从酵母到人类的进化过程中高度保守，且该通路与人类癌症的发生密切相关。
5. 人类merlin同源基因（NF2）是确凿的肿瘤抑制基因，在遗传性癌症综合征2型神经纤维瘤病中存在突变。warts、salvador、mats（作为肿瘤抑制因子的mob）、dRASSF（Ras关联家族）和yorkie的同源基因也被证实与哺乳动物肿瘤发生相关。
6. SWH通路的重要靶基因包括周期蛋白E（驱动细胞增殖）、DIAP1（抑制细胞凋亡）和bantam微RNA。该通路还通过明显的调控反馈环路控制expanded和four-jointed的表达。
7. 调控SWH通路活性的潜在过程包括：Expanded的表达及亚细胞定位修饰、Warts表达水平的调节，以及Yorkie的磷酸化。

英文摘要：

Intense research over the past four years has led to the discovery and characterization of a novel signalling network, known as the Salvador–Warts–Hippo (SWH) pathway, involved in tissue growth control in Drosophila melanogaster. At present, eleven proteins have been implicated as members of this pathway, and several downstream effector genes have been characterized. The importance of this pathway is emphasized by its evolutionary conservation, and by increasing evidence that its deregulation occurs in human tumours. Here, we review the main findings from Drosophila and the implications that these have for tumorigenesis in mammals.

摘要翻译： 

过去四年的深入研究揭示并鉴定了一种全新的信号网络，即Salvador–Warts–Hippo（SWH）通路，该通路参与果蝇的组织生长调控。目前，已有11种蛋白被确认为该通路的成员，并且多个下游效应基因也已被鉴定。该通路的重要性不仅体现在其在进化上的保守性，还体现在越来越多的证据表明其失调与人类肿瘤的发生有关。本文综述了果蝇研究中的主要发现，以及这些发现对哺乳动物肿瘤发生的意义。

原文链接：

The Salvador–Warts–Hippo pathway — an emerging tumour-suppressor network