文章：

利用黑腹果蝇绘制人类癌症路径图

Using Drosophila melanogaster to map human cancer pathways

原文发布日期：2005-07-20

DOI: 10.1038/nrc1671

类型: Review Article

开放获取: 否

要点：

1. The conservation of signalling pathways in Drosophila melanogaster enables modelling of most of the hallmarks of mammalian cancer, except telomere maintenance and angiogenesis.
2. Misregulation of most genes/pathways result in only 1–2 of the hallmarks of cancer, and in many cases overgrowth is restrained due to compensatory mechanisms.
3. Misregulation of genes/signalling pathways in clones of cells within a wild-type background can trigger non-cell-autonomous compensatory effects on the surrounding normal tissue, thereby maintaining tissue-size homeostasis.
4. Models of cell migration in D. melanogaster have uncovered novel potential invasion/metastasis genes.
5. Homozygous mutants of the neoplastic tumour suppressors scribble (scrib), discs large 1 (dlg1) and lethal (2) giant larvae (l(2)gl) exhibit most of the hallmarks of cancer, including the ability to invade/metastasize.
6. A new generation of screens attempt to model the development of mammalian tumours by analysing the cooperation of tumour suppressors and oncogenes in clones within an otherwise normal fly. These screens revealed that while scrib-mutant clones alone do not overgrow, strong cooperation is observed between scrib mutants and oncogenic Ras or Notch, resulting in invasive neoplastic tumours. Mutations in other cell-polarity genes also have a crucial role in restraining the pro-tumorigenic effects of oncogenic Ras.

要点翻译：

1. 黑腹果蝇信号通路的保守性使其能够模拟哺乳动物癌症的大部分特征，但端粒维持和血管生成除外。
2. 大多数基因/通路的失调仅导致1-2种癌症特征，且在多数情况下，由于补偿机制的存在，过度生长受到抑制。
3. 在野生型背景下的细胞克隆中，基因/信号通路的失调可对周围正常组织触发非细胞自主性补偿效应，从而维持组织大小的稳态。
4. 果蝇细胞迁移模型揭示了新的潜在侵袭/转移基因。
5. 癌性肿瘤抑制基因scribble（scrib）、discs large 1（dlg1）和lethal (2) giant larvae（l(2)gl）的纯合突变体表现出癌症的大部分特征，包括侵袭/转移能力。
6. 新一代筛选试图通过分析正常果蝇体内肿瘤抑制基因与癌基因在细胞克隆中的协同作用，模拟哺乳动物肿瘤的发展。这些筛选发现，虽然scrib突变克隆单独不会过度生长，但scrib突变与致癌Ras或Notch之间存在强协同作用，导致侵袭性癌性肿瘤的产生。其他细胞极性基因的突变在抑制致癌Ras的促肿瘤效应中也起关键作用。

英文摘要：

The development of human cancer is a multistep process, involving the cooperation of mutations in signalling, cell-cycle and cell-death pathways, as well as interactions between the tumour and the tumour microenvironment. To dissect the steps of tumorigenesis, simple animal models are needed. This article discusses the use of the genetically amenable, multicellular organism, the vinegar fly Drosophila melanogaster. In particular, recent studies have highlighted the power of D. melanogaster for examining cooperative interactions between tumour suppressors and oncogenes and for generating in vivo models of tumour development and metastasis.

摘要翻译： 

人类癌症的发生是一个多步骤的过程，涉及信号传导、细胞周期和细胞死亡通路中突变的协同作用，以及肿瘤与肿瘤微环境之间的相互作用。为了解析肿瘤发生的各个步骤，需要简单的动物模型。本文探讨了遗传操作便利的多细胞生物——果蝇（Drosophila melanogaster）的应用。特别是，近期研究强调了果蝇在研究抑癌基因与癌基因之间协同作用，以及建立肿瘤发展和转移的体内模型方面的强大能力。

原文链接：

Using Drosophila melanogaster to map human cancer pathways