In conclusion, our findings revealed that enhanced GAA anabolism, induced by 3D epigenome reprogramming, could promote PDAC liver metastasis by promoting c-Myc-mediated HMGA protein expression and reprogramming transcription-activating histone modification, indicating a close and complicated relationship between two important hallmarks of cancer — metabolic remodelling and epigenetic reprogramming — during pancreatic cancer liver metastasis. Here, MYC is linked to familial pancreatic carcinoma.