Genomic analysis of metastasis reveals an essential role for RhoC

被引:1202
作者
Clark, EA
Golub, TR
Lander, ES
Hynes, RO
机构
[1] MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA
[2] MIT, Dept Biol, Cambridge, MA 02139 USA
[3] Whitehead Inst MIT Ctr Genome Res, Cambridge, MA 02142 USA
[4] Dana Farber Canc Inst, Boston, MA 02115 USA
关键词
D O I
10.1038/35020106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:532 / 535
页数:4
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