• Higher levels of UGDH in more invasive malignant BC patient samples• Overexpression of EMT TF increased expression of UGDH• Depleting UDP-GlcUA inhibited mesenchymal phenotypes including cellular invasion and colony formation in vitro and metastatic phenotype in vivo• HA rescued UGDH KD phenotype• Fatty acid metabolism and PPAR-gamma pathway altered by UGDH KD. Here, UGDH is linked to breast cancer.