The present study uncovers a new EZH2/PTEN/E2F1 axis that participates in the regulation of the Akt/mTOR pathway and is responsible for the modulation of programmed cell death, as supported by our previous result [18], which also explains why cancer cells with ARID1A deficiency would be sensitive to EZH2 inhibitors. This evidence concerns the gene E2F1 and cancer.