Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

Abstract

Moving Signals: Many types of human breast cancers overexpress a cell-surface receptor—EphA2—a tyrosine kinase activated by the ligand ephrin-A1 present on adjoining cells. Salaita et al. (p. 1380 ; see the Perspective by Paszek and Weaver ) studied the regulation of mechanically stimulated EphA2 signaling by inducing intermembrane signaling between living EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. When the receptors engaged their ligands, they formed clusters that moved radially to the junction between the cells and the membranes. Physically impeding this movement altered the cellular response to ephrin-A1. Different breast cancer cell lines showed differences in receptor movement that correlated with their invasion potential, and might indicate their capacity for metastasis formation.