Mechanical control of cell migration by the metastasis suppressor tetraspanin cd82/kai1

Abstract

The plasma membrane is a key actor of cell migration. For instance, its tension controls persistent cell migration and cell surface caveolae integrity. Then, caveolae constituents such as caveolin‐1 can initiate a mechanotransduction loop that involves actin‐ and focal adhesion‐dependent control of the mechanosensor YAP to finely tune cell migration. Tetraspanin CD82 (also named KAI‐1) is an integral membrane protein and a metastasis suppressor. Its expression is lost in many cancers including breast cancer. It is a strong inhibitor of cell migration by a little‐known mechanism. We demonstrated here that CD82 controls persistent 2D migration of EGF‐induced single cells, stress fibers and focal adhesion sizes and dynamics. Mechanistically, we found that CD82 regulates membrane tension, cell surface caveolae abundance and YAP nuclear translocation in a cave-olin‐1‐dependent manner. Altogether, our data show that CD82 controls 2D cell migration using membrane‐driven mechanics involving caveolin and the YAP pathway.