All these results indicate that high CFL1 expression could enhance the nuclear translocation of Nrf2 via impairing the Keap1–Nrf2 interaction to promote PHGDH transcription, which could thus promote serine synthesis and metabolism to accelerate the production of antioxidative NADH and NADPH for scavenging the excessive ROS triggered by sorafenib, ultimately leading to the weakened sorafenib sensitivity of HCC cells (Figure 5J). The gene discussed is PHGDH; the disease is hepatocellular carcinoma.