Ephrin-A1 Regulates Cell Remodeling and Migration

Abstract

The Eph family of receptor tyrosine kinases and their cognate ligands, the Ephrins, form a coordinated program of cell contact-mediated migration control, polarity establishment, and tissue architecture development. Specifically, the ligand Ephrin-A1 has been shown to regulate cell morphology and motility through the activation of EphA receptors, which signal to the PI3K pathway to induce cell retraction. MEFs with PI3K subunit p85b knockout (p85b À/À ) exhibited markedly reduced cell retraction following Ephrin-A1 stimulation. Ephrin-A1 also serves as an inhibitory substrate for cell spreading and migration. Moreover, Ephrin-A1 treatment results in the dephosphorylation of paxillin and induces the reorganization of phosphopaxillin-containing focal adhesions. The Ephrin-A1 regulated paxillin dephosphorylation is phosphatase dependent, but p85b independent. The present study serves to demonstrate a novel molecular signaling pathways that regulate Ephrin-A1-regulated cell retraction and interaction to the substrate.

The effect of ephrin-A1 on resistance to Photofrin-mediated photodynamic therapy in esophageal squamous cell carcinoma cells

“…Therefore, the effect of ephrin-A1 on Photofrin-PDT is not mediated by inducing proliferation of ESCC. Studies have also suggested that ephrin-A1 regulates cell remodeling and migration in NIH3T3 cells [39]; however, it promotes the motility of EphA2-positive human cardiac stem cells and enhances cardiac repair [40]. The effect of ephrin-A1 on cellular events in ESCC, however, remains largely unknown.…”

Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility

“…Consistent with this, EphA2-deficient cells from knockout mice exhibit significantly reduced invasion and migration potential (7). On the other hand, activation of EphA2 by ephrinA1 ligand has been shown to attenuate Ras activation (8), suppress the Akt-mTORC1 pathway (9), and inhibit cell migration (10)(11)(12). As a possible resolution to this apparent contradiction, recent studies have suggested a ligand-independent mechanism that activates EphA2 promigratory signaling (13)(14)(15)(16).…”

“…In this study, we combined microfabrication, live imaging, and single-molecule tracking to directly map the signal transduction from ephrinA1: EphA2 complex to integrin adhesions, and revealed a spatially controlled mechanism for EphA2-integrin signaling cross talk. leads to dephosphorylation of focal adhesion kinase (FAK) and exerts a negative influence on integrin-mediated adhesions (10)(11)(12)(23)(24)(25). In other studies, activated EphA2 and other Eph receptors have been reported to enhance phosphorylation of FAK and promote cell spreading (26)(27)(28)(29).…”