Table 1.

NFE2L2 target genes involved in the regulation of ferroptosis in cancer cells

Name	General function	Role in ferroptosis	Tumor type	Ref.
NQO1	Detoxification of quinones	Anti-ferroptotic by reducing ROS and protecting against lipid peroxidation	HCC, lung, pancreatic, and other cancers	[6]
HMOX1	Degradation of heme to biliverdin, iron, and CO	Dual role: promotes ferroptosis through free iron release, but can protect through antioxidant effects	Multiple cancers	[6,74-76]
FTH1	Iron storage	Anti-ferroptotic by sequestering free iron and preventing ROS formation	Multiple cancers	[6]
FTL	Iron storage	Works with FTH1 to prevent ferroptosis by reducing free iron levels	Multiple cancers	[6]
HERC2	E3 ubiquitin ligase regulating NCOA4 degradation	Anti-ferroptotic by inhibiting ferritinophagy, reducing iron availability	HCC	[81]
SLC40A1	Iron exporter	Anti-ferroptotic by reducing intracellular iron levels	Breast, neuroblastoma	[82,83]
ABCB6	Transport of porphyrins and detoxification	Inhibits ferroptosis by protecting cells from oxidative damage	Multiple myeloma	[88]
FECH	Heme synthesis	Inhibition leads to ferroptosis through reduced heme availability	Lung cancer	[89]
PIR	Oxidative stress response	Anti-ferroptotic by reducing DNA damage and inhibiting HMGB1 release	Pancreatic cancer	[92]
MT1G	Metal ion homeostasis and detoxification	Anti-ferroptotic by preventing lipid peroxidation	HCC, renal cell carcinoma	[94]
SLC7A11	Cystine/glutamate antiporter	Anti-ferroptotic by promoting GSH synthesis and ROS neutralization	Ovarian, esophageal, lung	[100,102,103]
GCL	Glutamate-cysteine ligase, GSH synthesis	Anti-ferroptotic by increasing GSH levels	Multiple cancers	[107]
GSS	GSH synthetase, GSH synthesis	Anti-ferroptotic by increasing GSH synthesis	Multiple cancers	[107]
GSR	GSH reductase, GSH regeneration	Anti-ferroptotic by regenerating reduced GSH	Multiple cancers	[107]
GPX4	Reduces lipid peroxides	Anti-ferroptotic by preventing lipid peroxidation	Multiple cancers	[113]
AIFM2	NAD(P)H oxidoreductase	Anti-ferroptotic by reducing CoQ10 and maintaining plasma membrane integrity	Lung, pancreatic, HCC	[30,31]
MGST1	Microsomal GSH S-transferase	Anti-ferroptotic by detoxifying lipid peroxidation products	Pancreatic, gastric, uterine	[116]
ALDH1A1	Detoxification of aldehydes	Anti-ferroptotic by detoxifying lipid peroxidation products	Breast, lung, cervical	[123]
ALDH3A1	Detoxification of aldehydes	Anti-ferroptotic by detoxifying lipid peroxidation products	Glioblastoma, colorectal	[123]
G6PD	NADPH production in the pentose phosphate pathway	Anti-ferroptotic by providing NADPH for GSH regeneration	Renal cell carcinoma, HCC	[129]

NFE2L2: NFE2-like basic leucine zipper transcription factor 2; NQO1: quinone oxidoreductase-1; ROS: reactive oxygen species; HCC: hepatocellular carcinoma; HMOX1: heme oxygenase 1; FTH1: ferritin heavy chain 1; FTL: ferritin light chain; HERC2: HECT and RLD domain containing E3 ubiquitin protein ligase 2; NCOA4: nuclear receptor coactivator 4; SLC40A1: solute carrier family 40 member 1; ABCB6: ATP binding cassette subfamily B member 6; FECH: ferrochelatase; PIR: pirin; HMGB1: high mobility group box 1; MT1G: metallothionein 1G; SLC7A11: solute carrier family 7 member 11; GSH: glutathione; GCL: glutamate-cysteine ligase; GSS: glutathione synthetase; GSR: glutathione reductase; GPX4: glutathione peroxidase 4; AIFM2: apoptosis-inducing factor mitochondria-associated 2; CoQ10: coenzyme Q10; MGST1: microsomal GSH S-transferase 1; G6PD: glucose-6-phosphate dehydrogenase; NADPH: nicotinamide adenine dinucleotide phosphate.