Association between Gαi2 and ELMO1/Dock180 connects chemokine signalling with Rac activation and metastasis

Hongyan Li, Lei Yang, Hui Fu, Jianshe Yan, Ying Wang, Hua Guo, Xishan Hao, Xuehua Xu, Tian Jin () and Ning Zhang ()
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Hongyan Li: Tianjin Medical University Cancer Institute and Hospital and Research Center of Basic Medical Sciences
Lei Yang: Tianjin Medical University Cancer Institute and Hospital and Research Center of Basic Medical Sciences
Hui Fu: Tianjin Medical University Cancer Institute and Hospital and Research Center of Basic Medical Sciences
Jianshe Yan: Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Ying Wang: Beichen Hospital
Hua Guo: Tianjin Medical University Cancer Institute and Hospital and Research Center of Basic Medical Sciences
Xishan Hao: Tianjin Medical University Cancer Institute and Hospital and Research Center of Basic Medical Sciences
Xuehua Xu: Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Tian Jin: Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Ning Zhang: Tianjin Medical University Cancer Institute and Hospital and Research Center of Basic Medical Sciences

Nature Communications, 2013, vol. 4, issue 1, 1-12

Abstract: Abstract The chemokine CXCL12 and its G-protein-coupled receptor CXCR4 control the migration, invasiveness and metastasis of breast cancer cells. Binding of CXCL12 to CXCR4 triggers activation of heterotrimeric Gi proteins that regulate actin polymerization and migration. However, the pathways linking chemokine G-protein-coupled receptor/Gi signalling to actin polymerization and cancer cell migration are not known. Here we show that CXCL12 stimulation promotes interaction between Gαi2 and ELMO1. Gi signalling and ELMO1 are both required for CXCL12-mediated actin polymerization, migration and invasion of breast cancer cells. CXCL12 triggers a Gαi2-dependent membrane translocation of ELMO1, which associates with Dock180 to activate small G-proteins Rac1 and Rac2. In vivo, ELMO1 expression is associated with lymph node and distant metastasis, and knocking down ELMO1 impairs metastasis to the lung. Our findings indicate that a chemokine-controlled pathway, consisting of Gαi2, ELMO1/Dock180, Rac1 and Rac2, regulates the actin cytoskeleton during breast cancer metastasis.

Date: 2013
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DOI: 10.1038/ncomms2680

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