Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism

Nao Hiramoto-Yamaki, Shingo Takeuchi, Shuhei Ueda, Kohei Harada, Satoshi Fujimoto, Manabu Negishi, Hironori Katoh

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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 cortactinrich 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.

Original languageEnglish
Pages (from-to)461-477
Number of pages17
JournalJournal of Cell Biology
Volume190
Issue number3
DOIs
Publication statusPublished - Aug 9 2010
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Cell Biology

Cite this

Hiramoto-Yamaki, N., Takeuchi, S., Ueda, S., Harada, K., Fujimoto, S., Negishi, M., & Katoh, H. (2010). Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism. Journal of Cell Biology, 190(3), 461-477. https://doi.org/10.1083/jcb.201005141