The increased level of ManNAc resulted in ST6Gal1 upregulation that led to increased α2,6-sialylation.RNA-seq data also showed that the ABCG2-positive subpopulation originally expressed higher levels of ST6Gal1, and our overexpression and knockdown studies revealed that ST6Gal1 crucially regulates the invasion ability of pancreatic cancer cells, especially in the ABCG2-positive subpopulation. Here, ST6GAL1 is linked to familial pancreatic carcinoma.