文章：

Gli和hedgehog基因在肿瘤、胚胎和干细胞中的作用

Gli and hedgehog in cancer: tumours, embryos and stem cells

原文发布日期：2002-05-01

DOI: 10.1038/nrc796

类型: Review Article

开放获取: 否

要点：

1. The Sonic hedgehog (Shh) signal-transduction pathway is involved in the patterning, growth and survival of many cells and tissues, and its deregulation has been implicated in several cancers.
2. The pathway culminates in the activation of transcription factors of the Gli family. There are three such Gli proteins in vertebrates, with partially redundant functions, and Gli1 and Gli2 — both of which can mediate Hh signals — have been implicated in tumorigenesis.
3. The first hint that GLI1 activation might be involved in familial tumours came from the discovery that patched (PTCH, known as Ptc in mice), which inhibits the positive activation of GLI1, is mutated in basal-cell nevus syndrome (Gorlin's
4. a hereditary predisposition to basal-cell carcinomas, medulloblastomas and some other tumour types. This results in overexpression of positively activating GLI1 function.
5. The Shh–Gli pathway is also abnormally activated in sporadic cancers, including basal-cell carcinomas and medulloblastomas. Moreover, there is some evidence that Gli activation might be involved in the development of glioma and some other tumour types. Inhibition of Gli function might be a promising therapeutic target in these tumours.
6. In normal tissues, Gli is mainly active in precursor cells. This raises the possibility that tumours are derived from such cells, possibly even stem cells, which are unable to differentiate and/or to stop proliferating.

要点翻译：

1. Sonic hedgehog（Shh）信号转导通路参与多种细胞和组织的模式形成、生长与存活，其失调与多种癌症的发生相关。
2. 该通路最终激活Gli家族的转录因子。脊椎动物中存在三种功能部分冗余的Gli蛋白，其中既能介导Hh信号的Gli1和Gli2已被证实与肿瘤发生相关。
3. 首个提示GLI1激活可能参与家族性肿瘤的线索来自patched（PTCH，小鼠中称为Ptc）的发现——该蛋白能抑制GLI1的阳性激活作用，而在基底细胞痣综合征（Gorlin综合征）患者中发现该基因突变。
4. 这种遗传易感综合征会导致基底细胞癌、髓母细胞瘤及其他某些肿瘤类型的发生，最终引起具有阳性激活作用的GLI1功能过度表达。
5. Shh-Gli通路在散发性癌症（包括基底细胞癌和髓母细胞瘤）中也存在异常激活。此外，有证据表明Gli激活可能参与胶质瘤及其他某些肿瘤类型的发展进程。抑制Gli功能可能成为这些肿瘤极具前景的治疗靶点。
6. 在正常组织中，Gli主要在前体细胞中活跃。这提示肿瘤可能源于此类细胞（甚至可能是干细胞），这些细胞无法正常分化或停止增殖。

英文摘要：

Do tumours arise from stem cells, or are they derived from more differentiated cells that, for some reason, begin to recapitulate developmental programmes? Inappropriate activation of the Sonic hedgehog–Gli signalling pathway occurs in several types of tumour, including those of the brain and the skin. Studies in these and other systems suggest that inappropriate function of the Gli transcription factors in stem or precursor cells might lead to the onset of a tumorigenic programme and that these factors are prime targets for anticancer therapies.

摘要翻译： 

肿瘤是起源于干细胞，还是源自某些原因开始重演发育程序的更分化细胞？包括脑瘤和皮肤瘤在内的多种肿瘤中，均出现Sonic hedgehog–Gli信号通路的不当激活。对这些及其他系统的研究表明，Gli转录因子在干细胞或前体细胞中的异常功能可能启动肿瘤发生程序，因而这些因子是抗癌治疗的首要靶点。

原文链接：

Gli and hedgehog in cancer: tumours, embryos and stem cells