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

• DOI: 10.1073/pnas.1719961115
• Publication Date: 2018-06-04T19:06:30Z
• Authors: Zhongwen Chen; Dongmyung Oh; Kabir H. Biswas; Cheng-Han Yu; Ronen Zaidel-Bar; Jay T. Groves
• Keywords: 0301 basic medicine; Focal Adhesions; Receptor, EphA2; Lipid Bilayers; Ephrin-A1; Myosins; Ligands; Up-Regulation; 03 medical and health sciences; src-Family Kinases; Cell Movement; Cell Line, Tumor; Cell Adhesion; Humans; Paxillin; Phosphorylation; Signal Transduction

SignificanceCell receptors are neither uniformly distributed nor uniformly activated across plasma membrane. However, very little is known about how their spatial arrangement affects cellular response to receptor signaling. EphA2 is a receptor tyrosine kinase whose activation depends on binding of EphrinA1 ligands on the opposing cell, and EphA2 signaling plays an important role in cancer metastasis. In adherent cells, integrin adhesions are a key element to regulate cell–matrix interactions and cell migration. However, our understanding of how their activities are spatiotemporally coordinated remains superficial. 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.