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  • Original Paper
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Motility and invasion are differentially modulated by Rho family GTPases

Oncogene volume 19, pages 580–591 (2000)Cite this article

Abstract

Cell migration in vivo often requires invasion through tissue matrices. Currently little is known regarding the signaling pathways that regulate cell invasion through three-dimensional matrices. The small GTPases Cdc42, Rac and Rho are key regulators of actin cytoskeletal and adhesive structures. We now show that expression of dominant negative forms of either Cdc42, Rac or Rho inhibited PDGF-BB-stimulated Rat1 fibroblast invasion into 3D collagen matrices, indicating that the activity of each of these GTPases is necessary for cell invasion. In contrast, only Rac activation was required for PDGF-BB-stimulated locomotion across a planar substrate in the Boyden chamber. Interestingly, PDGF-induced invasion was also strongly inhibited by expression of constitutively active forms of Cdc42 or Rho, and to a lesser extent by constitutively active Rac. We also show that constitutively active V12-Rac significantly stimulated basal Rat1 fibroblast invasion, independent of PI-3-kinase activity, and that this effect was suppressed by the effector mutant V12/H40-Rac. These results suggest that cellular invasion may require an optimal level of activation of Cdc42, Rho and Rac, and that migration and invasion are differentially modulated by Rho family GTPases.

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Acknowledgements

This work was supported by grants CA37393 and CA45548 from the National Institute of Health. We thank Dr Rong-Guo Qiu for establishment of stable transfectant cell lines and Alan Flint (Howard Hughes Medical Facility, Children's Hospital, Boston), for FACS of GFP-transfected cells.

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  1. Bela Anand-Apte

    Present address: Department of Cell Biology, Cleveland Clinic Research Institute, 9500 Euclid Avenue, Cleveland, 44195, OH, USA

Authors and Affiliations

  1. Department of Surgical Research, Enders 1074, Children's Hospital, Harvard Medical School, Boston, 02115, Massachusetts, MA, USA

    Jacqueline Banyard, Bela Anand-Apte & Bruce R Zetter

  2. Laboratory of Molecular Oncology, Picower Institute for Medical Research, Manhasset, 11030, New York, NY, USA

    Marc Symons

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Banyard, J., Anand-Apte, B., Symons, M. et al. Motility and invasion are differentially modulated by Rho family GTPases. Oncogene 19, 580–591 (2000). https://doi.org/10.1038/sj.onc.1203338

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