Fig. 3

Signaling pathways regulating ferroptosis in prostate cancer. PKC represses Fe²⁺ uptake by promoting HSPB1 phosphorylation, thus decreasing lipid ROS production. DECR1 is negatively associated with PUFAs, but positively associated with the expression of GPX4, affecting ferroptosis through the ROS. CHAC1 increases the intracellular lipid peroxides levels by inhibiting the GPX4 levels. SREBP1/SCD1, which are promoted by the PI3K/AKT/mTOR pathway, contributes to the suppression of ROS, resulting in mitigating ferroptosis. SLC7A11, a cystine/glutamate antiporter that imports cystine into cells while exporting glutamate, decreases lipid ROS by enhancing GSH levels. SLC7A11 can be also upregulated by PANX2 that mediated by Nrf2, a major regulator of the antioxidant response. Mitochondrial dysregulation plays a critical role in promoting ferroptosis. Iron chelator inhibits ferroptosis by suppressing Fe²⁺, while erastin, RSL3, and buthionine sulfoximine induces ferroptosis by enhancing lipid ROS. ROS locates on the central position of multiple ferroptosis-related genes. ROS reactive oxygen species, PKC protein kinase C, HSPB1 heat shock protein family B member 1, DECR1 2,4-dienoyl-CoA reductase 1, DECR1 ChaC glutathione specific γ‑glutamylcyclotransferase 1, PUFAs polyunsaturated fatty acid, GPX4 glutathione peroxidase 4, PI3K-AKT phosphatidylinositol 3-kinase-serine/threonine kinase AKT, SREBP1 sterol regulatory element-binding proteins 1, SCD1 stearoyl-coenzyme A desaturase 1, GSH glutathione, Nrf2 nuclear factor erythroid 2-related factor 2, SLC7A11 solute carrier family 7 member 11