Edwards P A
Department of Pathology, University of Cambridge, UK.
Cancer Metastasis Rev. 1999;18(2):175-80. doi: 10.1023/a:1006304821464.
In recent years developmental biology has contributed a great deal to cancer research. This is in part because both fields address the question of how genes control the three-dimensional organisation of tissues, and how mutation of genes alters this. But also in recent years, the discovery that signalling pathways are conserved from worms to man, combined with the power of developmental biology's model organisms, principally Drosophila and C. elegans, to reveal signalling pathways that control tissue growth and organisation, has had a huge impact. Examples of this are the subject of the reviews in this issue, including the EGF-receptor, Wnt/APC/catenin, TGF-beta/Smad and hedgehog/patched/smoothened pathways, all of which were discovered and/or pieced together in model organisms, and all of which are disrupted by mutation in human cancer. Other topics considered are the control and execution of apoptosis; the search for tumour-suppressor-like genes in Drosophila; and genes of the Polycomb and Trithorax Groups that regulate the commitment of cells to patterns of differentiation, and that are among the targets for chromosome translocations. These stories illustrate how developmental biology has shown that there are many more signalling pathways relevant to neoplasia than the receptor tyrosine kinase pathways that first dominated the field; and that the signalling is more than just mitogenic or anti-mitogenic, and should be viewed as providing cells with information about their position and neighbours, that determines their role, differentiation and behaviour.
近年来，发育生物学对癌症研究贡献巨大。部分原因在于这两个领域都探讨了基因如何控制组织的三维结构，以及基因的突变如何改变这种结构。而且近年来，信号通路从蠕虫到人类都具有保守性这一发现，再加上发育生物学模式生物（主要是果蝇和秀丽隐杆线虫）揭示控制组织生长和结构的信号通路的强大能力，产生了巨大影响。本期综述的主题就是这方面的例子，包括表皮生长因子受体、Wnt/APC/连环蛋白、转化生长因子-β/Smad和刺猬索尼克蛋白/ patched / smoothened信号通路，所有这些都是在模式生物中发现和/或拼凑起来的，并且在人类癌症中都因突变而被破坏。还讨论了其他主题，如细胞凋亡的控制与执行；在果蝇中寻找肿瘤抑制样基因；以及多梳蛋白和三胸蛋白家族的基因，它们调节细胞向分化模式的定向分化，并且是染色体易位的靶点之一。这些事例说明发育生物学如何表明与肿瘤形成相关的信号通路比最初主导该领域的受体酪氨酸激酶通路要多得多；而且信号传导不仅仅是促有丝分裂或抗有丝分裂的，而应被视为为细胞提供有关其位置和邻居的信息，从而决定它们的作用、分化和行为。
