Mechanistically, the O-GlcNAcylation of PGK1 at Thr-255 not only increases PGK1 kinase activity to increase lactate production but also triggers the translocation of PGK1 into mitochondria to phosphorylate and inhibit pyruvate dehydrogenase in colon cancer cells. This evidence concerns the gene PGK1 and malignant colon neoplasm.