Integrin α11 mediates CCN1‐induced focal adhesion and β‐catenin translocation in esophageal epithelial cells

Background CCN1 is a matricellular protein that plays a critical role in several normal and pathological processes by signaling through different integrin receptors in a cell‐type specific manner. Clinical studies have suggested CCN1 as a putative marker for malignant progression towards esophageal adenocarcinoma. However, little is known about its signaling mechanisms in this tissue. The aim of this study was to determine the integrin receptor that mediates CCN1 actions in esophageal epithelial cells. Methods Esophageal epithelial cells were treated with recombinant CCN1 protein. Its effects on integrins were examined by microarray, real‐time PCR, immunoprecipitation, immunoblotting, and immunofluorescence microscopy. Results Out of all the known α‐ and β‐integrins, ITGA11 and ITGB5 were the only ones that responded to CCN1 treatment. Co‐immunoprecipitation assays demonstrated an association between integrin α11 and β5 in the presence of CCN1. Blocking either integrin subunit prevented CCN1‐induced focal adhesion and β‐catenin nuclear translocation. Taken together, these results provide evidence that integrin α11 can form a new partnership with β5 and that together they serve as a new receptor to mediate CCN1 actions in esophageal epithelial cells. This study was supported by the Department of Veterans Affairs of the United States and the American Heart Association.