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Genomic analysis of metastasis reveals an essential role for RhoC

Author

Listed:
  • Edwin A. Clark

    (Howard Hughes Medical Institute, Centre for Cancer Research
    Millennium Predictive Medicine)

  • Todd R. Golub

    (Whitehead Institute/MIT Centre for Genome Research
    Dana-Farber Cancer Institute)

  • Eric S. Lander

    (Massachusetts Institute of Technology
    Whitehead Institute/MIT Centre for Genome Research)

  • Richard O. Hynes

    (Howard Hughes Medical Institute, Centre for Cancer Research
    Massachusetts Institute of Technology)

Abstract

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 metastasis1. Relatively few genes have been implicated in these events2,3,4,5. 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.

Suggested Citation

  • Edwin A. Clark & Todd R. Golub & Eric S. Lander & Richard O. Hynes, 2000. "Genomic analysis of metastasis reveals an essential role for RhoC," Nature, Nature, vol. 406(6795), pages 532-535, August.
  • Handle: RePEc:nat:nature:v:406:y:2000:i:6795:d:10.1038_35020106
    DOI: 10.1038/35020106
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    Cited by:

    1. Eva Crosas-Molist & Vittoria Graziani & Oscar Maiques & Pahini Pandya & Joanne Monger & Remi Samain & Samantha L. George & Saba Malik & Jerrine Salise & Valle Morales & Adrien Le Guennec & R. Andrew A, 2023. "AMPK is a mechano-metabolic sensor linking cell adhesion and mitochondrial dynamics to Myosin-dependent cell migration," Nature Communications, Nature, vol. 14(1), pages 1-22, December.

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