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

Research output: Contribution to journalArticle

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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

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Cell Movement
Breast Neoplasms
Guanine Nucleotide Exchange Factors
Eph Family Receptors
Ephrins
Ligands
Epidermal Growth Factor
Neoplasms

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

Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism. / Hiramoto-Yamaki, Nao; Takeuchi, Shingo; Ueda, Shuhei; Harada, Kohei; Fujimoto, Satoshi; Negishi, Manabu; Katoh, Hironori.

In: Journal of Cell Biology, Vol. 190, No. 3, 09.08.2010, p. 461-477.

Research output: Contribution to journalArticle

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, vol. 190, no. 3, pp. 461-477. https://doi.org/10.1083/jcb.201005141
Hiramoto-Yamaki, Nao ; Takeuchi, Shingo ; Ueda, Shuhei ; Harada, Kohei ; Fujimoto, Satoshi ; Negishi, Manabu ; Katoh, Hironori. / Ephexin4 and EphA2 mediate cell migration through a RhoG-dependent mechanism. In: Journal of Cell Biology. 2010 ; Vol. 190, No. 3. pp. 461-477.
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