Since HIF-1α is absent in in vitro-cultured Dt81Hepa1-6 cells when maintained under normoxic conditions (data not shown), the elevated HIF-1α and GLUT-1 levels observed in vivo indicate that these cells are in a hypoxic environment with low O2 tension and that this environment could be responsible for the metabolic changes observed in these cells in vivo. In addition, tumor progression, angiogenesis and anaerobic metabolism enable cancer cells to survive under hypoxia as Hk II was shown to be selectively regulated through a HIF-1α-dependent mechanism [53, 54]. Here, HK2 is linked to cancer.