Proposed model describing the roles of Radil and KIF14 during cancer cell migration. (A) In highly motile cancer cells, KIF14 is up-regulated and sequesters Radil on microtubules. This enables optimal Radil–Rap1 signaling, inside-out integrin signaling, and cell–matrix adhesive properties required for efficient cell migration. (B) Depletion of Radil inhibits integrin activation, reduces cell–matrix adhesion, and causes loss of traction and cell motility. (C) Depletion of KIF14 leads to the release of Radil from microtubules, thereby increasing the pool of Radil available to associate with activated Rap1 at the plasma membrane. This leads to hyperactivated integrins, increases focal adhesion formation, and decreases motility.