Importantly, SEC63 only affected the binding of wild-type SMAD3 to the promoter of SNAI1 (Fig. 7K), suggesting that SEC63-associated acetylation of SMAD3 modulates SMAD3-mediated transcription of SNAI1. Together, these data suggest that SEC63-associated acetylation of SMAD3 epigenetically promotes the expression of Snail1 to facilitate HCC metastasis in the nucleus upon ER stress. Here, SNAI1 is linked to hepatocellular carcinoma.