Directional cell movement through tissues is critical for multiple biological 
processes and requires maintenance of polarity in the face of complex 
environmental cues. Here we use intravital imaging to demonstrate that secretion 
of exosomes from late endosomes is required for directionally persistent and 
efficient in vivo movement of cancer cells. Inhibiting exosome secretion or 
biogenesis leads to defective tumour cell migration associated with increased 
formation of unstable protrusions and excessive directional switching. In vitro 
rescue experiments with purified exosomes and matrix coating identify adhesion 
assembly as a critical exosome function that promotes efficient cell motility. 
Live-cell imaging reveals that exosome secretion directly precedes and promotes 
adhesion assembly. Fibronectin is found to be a critical motility-promoting 
cargo whose sorting into exosomes depends on binding to integrins. We propose 
that autocrine secretion of exosomes powerfully promotes directionally 
persistent and effective cell motility by reinforcing otherwise transient 
polarization states and promoting adhesion assembly.