Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. Signal., 20 September 2011
Vol. 4, Issue 191, p. ra60
[DOI: 10.1126/scisignal.2002221]

RESEARCH ARTICLES

Editor's Summary

Blocking Malignant Spread
Most deaths from cancer arise from the metastatic spread of malignant cells rather than from growth of the primary tumor itself. Thus, identifying the mechanisms whereby metastasis occurs—and thereby potential approaches to blocking it—represents a crucial element of cancer research. Noting that the chemokine receptor CXCR4 [chemokine (C-X-C motif) receptor 4], which mediates trafficking of hematopoietic cells, has been implicated in breast cancer metastasis, Yagi et al. explored the underlying mechanisms. They found that the CXCR4-mediated migration toward chemokine of a therapy-resistant class of breast cancer cell, unlike its mobilization of hematopoietic stem cells, depended on signaling through Gα13 of the Gα12/13 family of G proteins and of the small guanosine triphosphatase Rho. Moreover, fasudil, a Rho inhibitor now used to treat vasospasm and pulmonary hypertension, limited breast cancer metastasis from lymph nodes in a mouse model system. Thus, interfering with CXCR4-Gα13-Rho signaling may provide a therapeutic approach to blocking metastasis of this class of breast cancer without untoward side effects on the mobilization and migration of hematopoietic cells.

Citation: H. Yagi, W. Tan, P. Dillenburg-Pilla, S. Armando, P. Amornphimoltham, M. Simaan, R. Weigert, A. A. Molinolo, M. Bouvier, J. S. Gutkind, A Synthetic Biology Approach Reveals a CXCR4-G13-Rho Signaling Axis Driving Transendothelial Migration of Metastatic Breast Cancer Cells. Sci. Signal. 4, ra60 (2011).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
PDZ-RhoGEF and LARG Are Essential for Embryonic Development and Provide a Link between Thrombin and LPA Receptors and Rho Activation.
C. M. Mikelis, T. R. Palmby, M. Simaan, W. Li, R. Szabo, R. Lyons, D. Martin, H. Yagi, S. Fukuhara, H. Chikumi, et al. (2013)
J. Biol. Chem. 288, 12232-12243
   Abstract »    Full Text »    PDF »
CXCR4-Based Imaging Agents.
L. E. Woodard and S. Nimmagadda (2011)
J. Nucl. Med. 52, 1665-1669
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 20 September 2011.
J. S. Gutkind and A. M. VanHook (2011)
Science Signaling 4, pc19
   Abstract »    Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882