Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism.
Article Details
- CitationCopy to clipboard
Hiramoto-Yamaki N, Takeuchi S, Ueda S, Harada K, Fujimoto S, Negishi M, Katoh H
Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism.
J Cell Biol. 2010 Aug 9;190(3):461-77. doi: 10.1083/jcb.201005141. Epub 2010 Aug 2.
- PubMed ID
- 20679435 [ View in PubMed]
- Abstract
EphA2, a member of the Eph receptor family, is frequently overexpressed in a variety of human cancers, including breast cancers, and promotes cancer cell motility and invasion independently of its ligand ephrin stimulation. In this study, we identify Ephexin4 as a guanine nucleotide exchange factor (GEF) for RhoG that interacts with EphA2 in breast cancer cells, and knockdown and rescue experiments show that Ephexin4 acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. The activation of RhoG recruits its effector ELMO2 and a Rac GEF Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. In addition, the Dock4-mediated Rac activation is required for breast cancer cell migration. Our findings reveal a novel link between EphA2 and Rac activation that contributes to the cell motility and invasiveness of breast cancer cells.