Fig. 8.

Schematic summary displays that FCN3 deficiency in HCC causes the overactivation of IR-β and AKT, which further promotes the expression of the downstream transcription factor SREBP1c. Then, the expression of DNL and lipid desaturation related genes including ACC1, FASN and SCD1 are upregulated, resulting in increased intracellular MUFA, which promotes a ferroptosis-resistant cell state. In contrast, overexpression of FCN3 enhances lipid peroxidation through inhibiting IR-AKT-DNL axis and thereby sensitizes HCC cells to ferroptosis