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RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells

Oncogene volume 31, pages 4740–4749 (2012)Cite this article

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Abstract

Vesicular structures called microvesicles (MVs) that are shed from the surfaces of cancer cells are capable of transferring oncogenic cargo to recipient cancer cells, as well as to normal cells, sending mitogenic signals that greatly enhance tumor growth. Because MVs are stable in the circulation, they also may have a key role in secondary colonization and metastasis. Thus, understanding how MVs are generated could have important consequences for interfering with cancer progression. Here we report that the small GTPase RhoA triggers a specific signaling pathway essential for MV biogenesis in various human cancer cells. Inhibiting the activity of different proteins comprising this pathway blocks MV biogenesis in the donor cancer cells and prevents oncogenic transformation in cell culture as well as tumor growth in mice. Although RhoA has often been implicated in human cancer, these findings now highlight a previously unappreciated role for this GTPase in malignant transformation, and demonstrate that blocking MV biogenesis may offer novel approaches for interfering with malignant transformation.

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Acknowledgements

We thank Cindy Westmiller for her secretarial assistance and the NIH and the Komen Foundation for funding.

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Author notes

  1. B Li and M A Antonyak: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, NY, Ithaca, USA

    B Li, M A Antonyak, J Zhang & R A Cerione

  2. Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, NY, Ithaca, USA

    B Li & R A Cerione

Authors
  1. B Li
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  2. M A Antonyak
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  3. J Zhang
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  4. R A Cerione
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Correspondence to R A Cerione.

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Supplementary Information accompanies the paper on the Oncogene website

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Li, B., Antonyak, M., Zhang, J. et al. RhoA triggers a specific signaling pathway that generates transforming microvesicles in cancer cells. Oncogene 31, 4740–4749 (2012). https://doi.org/10.1038/onc.2011.636

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