L1CAM Knockout Cell Line (HEK293)

To move forward, cells must exert backward forces against their surrounding environment. Recent studies have highlighted the importance of integrin-independent forces for cell migration; however, the molecular machinery that exerts forces remains unclear. This study shows that the clutch-linker molecule shootin1 and the cell adhesion molecule L1 transmit the backward force of treadmilling actin filaments to the environment, enabling rapid dendritic cell migration. Notably, shootin1 and L1 transmit weak traction forces, up to ∼100 times weaker than integrin-based forces, by constituting an integrin-independent slippery adhesion-clutch. This adhesion-clutch is tunable in response to the chemoattractant CCL19 and the adhesive ligand laminin, thereby enabling chemotaxis and haptokinesis. Furthermore, aberrant activity of this adhesion-clutch enhances glioblastoma cell invasion. The results show that the weak adhesion-clutch is well-suited for rapid cell migration, without forming strong adhesions that impede cell motility, and provides a potential target for inhibiting abnormal tumor invasion.