In contrast with CRPC, where EZH2 expression seems to be independent of E2F1 levels,35 we have previously shown that E2F1 directly stimulates EZH2 expression in ACC.8 A reciprocal effect of EZH2 on E2F1 expression has been shown in hepatocellular carcinoma cells, where EZH2 repressed expression of E2F1, which may constitute a negative feedback loop.36 In contrast, we show that tampering with EZH2 expression/activity has no impact on E2F1 expression (Fig. 3d and Fig. S2D). Here, EZH2 is linked to hepatocellular carcinoma.