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Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion

Oncogene volume 24, pages 7821–7829 (2005)Cite this article

Abstract

Members of the Rho family of small GTPases have been shown to be involved in tumorigenesis and metastasis. Currently, most of the available information on the function of Rho proteins in malignant transformation is based on the use of dominant-negative mutants of these GTPases. The specificity of these dominant-negative mutants is limited however. In this study, we used small interfering RNA directed against either Rac1 or Rac3 to reduce their expression specifically. In line with observations using dominant-negative Rac1 in other cell types, we show that RNA interference-mediated depletion of Rac1 strongly inhibits lamellipodia formation, cell migration and invasion in SNB19 glioblastoma cells. Surprisingly however, Rac1 depletion has a much smaller inhibitory effect on SNB19 cell proliferation and survival. Interestingly, whereas depletion of Rac3 strongly inhibits SNB19 cell invasion, it does not affect lamellipodia formation and has only minor effects on cell migration and proliferation. Similar results were obtained in BT549 breast carcinoma cells. Thus, functional analysis of Rac1 and Rac3 using RNA interference reveals a critical role for these GTPases in the invasive behavior of glioma and breast carcinoma cells.

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Acknowledgements

We thank Dr L Van Aelst (Cold Spring Harbor) for the pCGT Rac1-V12 plasmid and SNB19 and U87MG cells. We also like to thank N Rusk and A Valster for critical reading of the manuscript. This work was supported by National Institutes of Health Grant CA87567.

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Authors and Affiliations

  1. Institute for Medical Research at North Shore-LIJ, 350 Community Drive, Manhasset, 11030, NY, USA

    Amanda Y Chan, Ya-yu Chuang & Marc Symons

  2. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, 10461, NY, USA

    Salvatore J Coniglio & Marc Symons

  3. Department of Medicine, New York University School of Medicine, New York, 10016, NY, USA

    David Michaelson & Mark R Philips

  4. Department of Cell Biology, New York University School of Medicine, New York, 10016, NY, USA

    David Michaelson & Mark R Philips

  5. Department of Immunology, The Scripps Research Institute, La Jolla, 92037, CA, USA

    Ulla G Knaus

  6. Department of Surgery, North Shore-Long Island Jewish Research Institute, Manhasset, 11030, NY, USA

    Marc Symons

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  1. Amanda Y Chan
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Correspondence to Marc Symons.

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Chan, A., Coniglio, S., Chuang, Yy. et al. Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion. Oncogene 24, 7821–7829 (2005). https://doi.org/10.1038/sj.onc.1208909

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