• KLF4 upregulates UGDH expression by methylating CpGs• UGDH required for KLF4-induced cell migration• UGDH KD decreases GAG abundance, cell proliferation and migration in vitro and tumor growth/ migration in vivo• UGDH KD a/w decreased expression of ECM proteins tenascin C, brevican. The gene discussed is UGDH; the disease is neoplasm.