A Synthetic Biology Approach Reveals a CXCR4-G(13)-RhoSignaling Axis Driving Transendothelial Migration of Metastatic Breast Cancer Cells

作者：Yagi Hiroshi; Tan Wenfu; Dillenburg Pilla Patricia; Armando Sylvain; Amornphimoltham Panomwat; Simaan May; Weigert Roberto; Molinolo Alfredo A; Bouvier Michel; Gutkind J Silvio^*

来源：Science Signaling, 2011, 4(191): ra60.

DOI：10.1126/scisignal.2002221

Tumor cells can co-opt the promigratory activity of chemokines and their cognate G protein-coupled receptors (GPCRs) to metastasize to regional lymph nodes or distant organs. Indeed, the migration toward SDF-1 (stromal cell-derived factor 1) of tumor cells bearing CXCR4 [chemokine (C-X-C motif) receptor 4] has been implicated in the lymphatic and organ-specific metastasis of various human malignancies. Here, we used chimeric G proteins and GPCRs activated solely by artificial ligands to selectively activate the signaling pathways downstream of specific G proteins and showed that CXCR4-mediated chemotaxis and transendothelial migration of metastatic basal-like breast cancer cells required activation of G alpha(13), a member of the G alpha(12/13) G protein family, and of the small guanosine triphosphatase Rho. Multiple complementary experimental strategies, including synthetic biology approaches, indicated that signaling-selective inhibition of the CXCR4-G alpha(13)-Rho axis prevents the metastatic spread of basal-like breast cancer cells.

• 出版日期2011-9-20