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Pathways of metastasis suppression in bladder cancer

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Abstract

Despite the recent advances in the diagnosis of bladder cancer, recurrence after surgical intervention for muscle invasive disease is still problematic as nearly half of the patients harbor occult distant metastases and this, in turn, is associated with poor 5-year survival rate. We have recently identified Rho family GDP dissociation inhibitor 2 (RhoGDI2) protein as functional metastasis suppressor and a prognostic marker in patients after cystectomy. In identifying the mechanisms underlying metastasis suppression by RhoGDI2, we found this protein to be associated with the c-Src kinase in human tumors, where the expression of both is diminished as a function of stage. Interestingly, c-Src bound to and phosphorylated RhoGDI2 resulting in enhanced metastasis suppressive potency. In this review, we will discuss the established roles of c-Src and RhoGDI2 in bladder cancer and speculate on their therapeutic relevance.

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Acknowledgments

This study was supported by NIH grant R01CA075115 to DT. The authors wish to thank Dr. Michael Harding for helpful suggestions. None of the authors have any financial conflict of interest that might be construed to influence the results or interpretation of the manuscript.

Competing interest statement

The authors declare that they have no competing financial interests.

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Authors and Affiliations

  1. Department of Urology, University of Virginia, Box 800422, Charlottesville, VA, 22908, USA

    Neveen Said & Dan Theodorescu

  2. Departments of Molecular Physiology and Biological Physics, University of Virginia, Box 800422, Charlottesville, VA, 22908, USA

    Dan Theodorescu

  3. Paul Mellon Urologic Cancer Institute, University of Virginia, Box 800422, Charlottesville, VA, 22908, USA

    Dan Theodorescu

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  1. Neveen Said
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  2. Dan Theodorescu
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Correspondence to Dan Theodorescu.

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Said, N., Theodorescu, D. Pathways of metastasis suppression in bladder cancer. Cancer Metastasis Rev 28, 327–333 (2009). https://doi.org/10.1007/s10555-009-9197-4

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