PIK3CA and cancer: Multiple tumor suppressors that repress PI3K/AKT/mTOR and HIF-1 signaling are epigenetically silenced by promoter hypermethylation, including PTEN126, 127, 128, 129, 130, LKB1,131, 132 VHL133, 134, 135, 136 and prolyl hydroxylases (PHD1/2/3).137, 138 Hence, differential DNA methylation significantly contributes to glycolytic phenotype in human cancers.