HIF1A and hepatocellular carcinoma: Because both PKM and EGLN3 (encoding PHD3) are HIF1a target genes, the positive feedback loop that promotes HIF1a activity maintains overexpression of PKM2 and other glycolytic genes [39], which accelerates metabolic reprogramming of cancer cells and may be an alternative salvage pathway to supply ATP to promote hypoxic HCC growth or survival.