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International Journal of Breast Cancer
Volume 2012, Article ID 124704, 5 pages
Review Article

RKIP Suppresses Breast Cancer Metastasis to the Bone by Regulating Stroma-Associated Genes

Ben May Department for Cancer Research, Gordon Center for Integrative Science, The University of Chicago, W421C, 929 East 57th Street, Chicago, IL 60637, USA

Received 26 September 2011; Accepted 21 November 2011

Academic Editor: Lalita Shevde

Copyright © 2012 Elena Bevilacqua et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In the past decade cancer research has recognized the importance of tumorstroma interactions for the progression of primary tumors to an aggressive and invasive phenotype and for colonization of new organs in the context of metastasis. The dialogue between tumor cells and the surrounding stroma is a complex and dynamic phenomenon, as many cell types and soluble factors are involved. While the function of many of the players involved in this cross talk have been studied, the regulatory mechanisms and signaling pathways that control their expression haven’t been investigated in depth. By using a novel, interdisciplinary approach applied to the mechanism of action of the metastasis suppressor, Raf kinase inhibitory protein (RKIP), we identified a signaling pathway that suppresses invasion and metastasis through regulation of stroma-associated genes. Conceptually, the approach we developed uses a master regulator and expression arrays from breast cancer patients to formulate hypotheses based on clinical data. Experimental validation is followed by further bioinformatic analysis to establish the clinical significance of discoveries. Using RKIP as an example we show here that this multi-step approach can be used to identify gene regulatory mechanisms that affect tumor-stroma interactions that in turn influence metastasis to the bone or other organs.