Exocyst controls exosome biogenesis via Rab11a

Tumor cells actively release large quantities of exosomes, which pivotally participate in the regulation of cancer biology, including head and neck cancer (HNC). Exosome biogenesis and release are complex and elaborate processes that are considered to be similar to the process of exocyst-mediated vesicle delivery. By analyzing the expression of exocyst subunits and their role in patients with HNC, we aimed to identify exocyst and its functions in exosome biogenesis and investigate the molecular mechanisms underlying the regulation of exosome transport in HNC cells. We observed that exocysts were highly expressed in HNC cells and could promote exosome secretion in these cells. In addition, downregulation of exocyst expression inhibited HN4 cell proliferation by reducing exosome secretion. Interestingly, immunofluorescence and electron microscopy revealed the accumulation of multivesicular bodies (MVBs) after the knockdown of exocyst. Autophagy, the major pathway of exosome degradation, is not activated by this intracellular accumulation of MVBs, but these MVBs are consumed when autophagy is activated under the condition of cell starvation. Rab11a, a small GTPase that is involved in MVB fusion, also interacted with the exocyst. These findings suggest that the exocyst can regulate exosome biogenesis and participate in the malignant behavior of tumor cells.

Automated summary

Tumor cells actively release large quantities of exosomes, which play important roles in the regulation of head and neck cancer (HNC). In this study, we investigated the expression and function of exocyst, a protein complex involved in exosome biogenesis, in HNC cells. We found that exocysts were highly expressed in HNC cells and could promote exosome secretion. In addition, downregulation of exocyst expression inhibited HNC cell proliferation. We also observed the accumulation of multivesicular bodies (MVBs) after exocyst knockdown, which were consumed when autophagy was activated. Our findings suggest that the exocyst can regulate exosome biogenesis and contribute to the malignant behavior of tumor cells.