Fig. 1

LSH-mediated inhibition of ferroptosis and enhancement of lung tumorigenesis. In this model, LSH acts as a novel inhibitor of ferroptosis by regulating several metabolism-related genes. LSH expression is up-regulated by c-Myc, which is enriched at the LSH promoter by the EGLN1-mediated repression of HIF-1α. The induced LSH interacts with WDR76, which, in turn, up-regulates the lipid metabolic genes including SCD1 and FADS2. These metabolic genes inhibit the accumulation of lipid ROS and intracellular iron, which are required for ferroptosis, and inhibition of ferroptosis by LSH ultimately promotes cancer progression. HIF-1α hypoxia-inducible factor-1α, EGLN1/3 Egl-9 family hypoxia-inducible factor 1/3, LSH lymphoid-specific helicase, WDR76 WD repeat-containing protein 76, SCD1 stearoyl-CoA desaturase 1, FADS2 fatty acid desaturase 2, ROS reactive oxygen species