Although most recent studies have shown that exosomes secreted from cancer cells downregulate ROS levels in recipient cells, Fu et al. suggested that exosomes derived from primary hepatocellular carcinoma can deliver both mRNA and protein of SMAD family member 3 (SMAD3) to circulating tumor cells (CTCs), thereby elevating intracellular ROS, dependent on the overexpression and activation of SMAD3, to facilitate CSC metastasis by promoting cell adhesion [61]. Here, SMAD3 is linked to hepatocellular carcinoma.