The Parkinson's disease‐associated protein α‐synuclein inhibits hepatoma by exosome delivery

Abstract Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer. However, their relevant pathogenesis is not clear. In the present study, we investigated the potential role of exosome‐delivered α‐synuclein (α‐syn) in the regulation between PD and liver cancer. We cultured hepatocellular carcinoma (HCC) cells with exosomes derived from conditioned medium of the PD cellular model, and injected exosomes enriched with α‐syn into the striatum of a liver cancer rat model. We found that α‐syn‐contained exosomes from the rotenone‐induced cellular model of PD suppressed the growth, migration, and invasion of HCC cells. Integrin αVβ5 in exosomes from the rotenone‐induced PD model was higher than that in the control, resulting in more α‐syn‐contained exosomes being taken up by HCC cells. Consistently, in vivo experiments with rat models also confirmed exosome‐delivered α‐syn inhibited liver cancer. These findings illustrate the important role of PD‐associated protein α‐syn inhibiting hepatoma by exosome delivery, suggesting a new mechanism underlying the link between these two diseases and therapeutics of liver cancer.