Sci. Signal., 20 September 2011
Blocking Malignant SpreadMost 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).
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