Crosstalk Between Adhesion Molecules Influences Cell Traction and Migration

Abstract

Cell migration is the major driver of invasion and metastasis during cancer progression. For cells to migrate, they utilize the actin-myosin cytoskeleton and adhesion molecules, such as integrins and CD44, to generate traction forces in their environment. Whereas CD44 primarily binds to hyaluronic acid (HA), integrins primarily bind to extracellular matrix proteins (ECM) such as collagen. However, the role of CD44 under integrin-mediated conditions, and vice versa, is not well known. Here we used TFM to assess the functional mechanical relationship between integrins and CD44. Performing TFM on integrin-mediated adhesion conditions, i.e., collagen, we found that CD44KO U251 cells exerted more traction force than wild-type (WT) U251 cells. When using untreated WT and CD44-blocked WT, we observed comparable results with CD44KO cells again showing an increase in traction force on collagen gels. Conversely, in CD44-mediated adhesive conditions, integrin-blocked WT cells exerted higher traction force than untreated WT cells. Our data suggests that CD44 and integrins have a mutually antagonistic relationship where one receptor represses the other’s ability to generate traction force on its cognate substrate.