Fig. 4
Signaling pathways regulating ferroptosis in RCC. DPP4 induces ferroptosis by binding to NOX1 and functioning in promoting ROS, while SUV39H1 downregulates the expression of DPP4. NCOA4 targeting FTH and FTMT thus increase the ferrous iron (Fe2+) and ROS. The Hippo effector TAZ enhances ROS via the EMP1-NOX4 signal axis. ACOT8 positively regulates GPX4 expression, but is negatively associated with TAZ and HIF-2α. HIF-2α upregulates by the VHL, and is positively associated with HILPDA to activate the expression of PUFAs, thus strengthens the accumulation of ROS. GPX1 participates in ROS metabolic process that suppressing ROS directly. In RCC, ferroptosis-inducing agents erastin and artesunate elevate the lipid ROS, thus promote ferroptotic cell death. NCOA4 nuclear receptor coactivator 4, FTH ferritin heavy chain, FTMT ferritin mitochondrial, GPX1 glutathione peroxidase-1, SUV39H1 suppressor of variegation 3–9 homolog 1, DPP4 dipeptidyl-peptidase-4, ACOT8 acyl-CoA thioesterase 8, VHL von Hippel-Lindau, HIF-2α a hypoxia-inducible factor, HILPDA hypoxia inducible lipid droplet associated protein, NOX4 nicotinamide adenine dinucleotide phosphate oxidase 4, EMP1 epithelial membrane protein 1, TAZ transcriptional coactivator with PDZ-binding motif