Genomic analysis of metastasis reveals an essential role for RhoC
Genomic analysis of metastasis reveals an essential role for RhoC
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DOI：
10.1038/35020106
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发表时间：
2000-08-03
期刊：
影响因子：
64.8
通讯作者：
Hynes, RO
中科院分区：
文献类型：
--
作者：
Clark, EA;Golub, TR;Hynes, RO
在癌症进展过程中，最具破坏性的变化是从局部生长的肿瘤转变为转移性的致命肿瘤。据信这种转变涉及众多改变，这些改变使肿瘤细胞能够完成转移所需的一系列复杂事件。在这些事件中所涉及的基因相对较少。在此我们利用一种体内选择方案来筛选高度转移性的黑色素瘤细胞。通过在DNA芯片上分析这些细胞，我们确定了一种与转移表型进展相关的基因表达模式。特别是，我们发现一些参与细胞外基质组装的基因以及另一组直接或间接调节基于肌动蛋白的细胞骨架的基因表达增强。其中一种，小GTP酶RhoC，在过度表达时会增强转移，而显性负性Rho则抑制转移。对表达显性负性Rho或RhoC的细胞表型分析表明，RhoC在肿瘤细胞侵袭中很重要。基因组学方法使我们能够识别参与一个过程的基因家族，而不仅仅是单个基因，并且能够表明哪些分子和细胞事件在诸如转移这样的复杂生物学过程中可能是重要的。
The most damaging change during cancer progression is the switch from a locally growing tumour to a metastatic killer. This switch is believed to involve numerous alterations that allow tumour cells to complete the complex series of events needed for metastasis(1). Relatively few genes have been implicated in these events(2-5.) Here we use an in vivo selection scheme to select highly metastatic melanoma cells. By analysing these cells on DNA arrays, we define a pattern of gene expression that correlates with progression to a metastatic phenotype. In particular, we show enhanced expression of several genes involved in extracellular matrix assembly and of a second set of genes that regulate, either directly or indirectly, the actin-based cytoskeleton. One of these, the small GTPase RhoC, enhances metastasis when overexpressed, whereas a dominant-negative Rho inhibits metastasis. Analysis of the phenotype of cells expressing dominant-negative Rho or RhoC indicates that RhoC is important in tumour cell invasion. The genomic approach allows us to identify families of genes involved in a process, not just single genes, and can indicate which molecular and cellular events might be important in complex biological processes such as metastasis.