RAB25 and cancer: We demonstrate that endogenous Rab25 vesicles coordinate the positioning of key cargos, including the actin regulator FMNL1 and integrin β1, with the activation of Rho guanosine triphosphatases at the plasma membrane to generate and maintain F-actin–rich filopodium-like protrusions and promote cancer cell invasive migration in the three-dimensional matrix.