Sun et al. found that exosome S100A4 derived from highly metastatic hepatocellular carcinoma cells promotes metastasis through activation of STAT3, and HCC patients with high plasma levels of exosome S100A4 also had a poorer prognosis, suggesting that exosome S100A4 is a new prognostic marker and therapeutic target for HCC metastasis (Sun et al. 2021). Here, STAT3 is linked to hepatocellular carcinoma.