In HCC, hypoxia is an extrinsic factor inducing phosphofructokinase-fructose bisphosphatase 4 (PFKFB4) expression in HCC in a HIF-1-dependent manner, which shifts the equilibrium from glycolysis to the PPP and alleviates cellular stress response, thus supporting HCC progression [93]. This evidence concerns the gene PFKFB4 and hepatocellular carcinoma.