The Hallmarks of Ferroptosis

Literature Cited

1. Abrams RP, Carroll WL, Woerpel KA 2016. Five-membered ring peroxide selectively initiates ferroptosis in cancer cells. ACS Chem. Biol. 11:51305–12
   [Google Scholar]
2. Agmon E, Solon J, Bassereau P, Stockwell BR 2018. Modeling the effects of lipid peroxidation during ferroptosis on membrane properties. Sci. Rep. 8:5155
   [Google Scholar]
3. Alvarez SW, Sviderskiy VO, Terzi EM, Papagiannakopoulos T, Moreira AL et al. 2017. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature 551:7682639–43
   [Google Scholar]
4. Anding AL, Baehrecke EH 2015. Autophagy in cell life and cell death. Curr. Top. Dev. Biol. 114:67–91
   [Google Scholar]
5. Bailey HH, Mulcahy RT, Tutsch KD, Arzoomanian RZ, Alberti D et al. 1994. Phase I clinical trial of intravenous l-buthionine sulfoximine and melphalan: an attempt at modulation of glutathione. J. Clin. Oncol. 12:1194–205
   [Google Scholar]
6. Bailey HH, Ripple G, Tutsch KD, Arzoomanian RZ, Alberti D et al. 1997. Phase I study of continuous-infusion l-S,R-buthionine sulfoximine with intravenous melphalan. J. Natl. Cancer Inst. 89:231789–96
   [Google Scholar]
7. Banjac A, Perisic T, Sato H, Seiler A, Bannai S et al. 2008. The cystine/cysteine cycle: a redox cycle regulating susceptibility versus resistance to cell death. Oncogene 27:111618–28
   [Google Scholar]
8. Basuli D, Tesfay L, Deng Z, Paul B, Yamamoto Y et al. 2017. Iron addiction: a novel therapeutic target in ovarian cancer. Oncogene 36:294089–99
   [Google Scholar]
9. Brumatti G, Ma C, Lalaoui N, Nguyen N-Y, Navarro M et al. 2016. The caspase-8 inhibitor emricasan combines with the SMAC mimetic birinapant to induce necroptosis and treat acute myeloid leukemia. Sci. Transl. Med. 8:339339ra69
   [Google Scholar]
10. Brown CW, Amante JJ, Goel HL, Mercurio AM 2017. The α6β4 integrin promotes resistance to ferroptosis. J. Cell Biol. 216:124287–97
    [Google Scholar]
11. Brown CW, Amante JJ, Mercurio AM 2018. Cell clustering mediated by the adhesion protein PVRL4 is necessary for α6β4 integrin–promoted ferroptosis resistance in matrix-detached cells. J. Biol Chem. In press
12. Bump EA, Yu NY, Brown JM 1982. Radiosensitization of hypoxic tumor cells by depletion of intracellular glutathione. Science 217:4559544–45
    [Google Scholar]
13. Calvert P, Yao KS, Hamilton TC, O'Dwyer PJ 1998. Clinical studies of reversal of drug resistance based on glutathione. Chem. Biol. Interact. 111–112:213–24
    [Google Scholar]
14. Cao JY, Dixon SJ 2016. Mechanisms of ferroptosis. Cell. Mol. Life Sci. 73:11–122195–209
    [Google Scholar]
15. Chen D, Tavana O, Chu B, Erber L, Chen Y et al. 2017. NRF2 is a major target of ARF in p53-independent tumor suppression. Mol. Cell 68:1224–32
    [Google Scholar]
16. Chen W, Sun Z, Wang X-J, Jiang T, Huang Z et al. 2009. Direct interaction between Nrf2 and p21^Cip1/WAF1 upregulates the Nrf2-mediated antioxidant response. Mol. Cell 34:6663–73
    [Google Scholar]
17. Chintala S, Li W, Lamoreux ML, Ito S, Wakamatsu K et al. 2005. Slc7a11 gene controls production of pheomelanin pigment and proliferation of cultured cells. PNAS 102:3110964–69
    [Google Scholar]
18. Chio IIC, Jafarnejad SM, Ponz-Sarvise M, Park Y, Rivera K et al. 2016. NRF2 promotes tumor maintenance by modulating mRNA translation in pancreatic cancer. Cell 166:4963–76
    [Google Scholar]
19. Conrad M, Kagan VE, Bayir H, Pagnussat GC, Head B et al. 2018. Regulation of lipid peroxidation and ferroptosis in diverse species. Genes Dev 32:602–19
    [Google Scholar]
20. Coriat R, Nicco C, Chéreau C, Mir O, Alexandre J et al. 2012. Sorafenib-induced hepatocellular carcinoma cell death depends on reactive oxygen species production in vitro and in vivo. Mol. Cancer Ther. 11:102284–93
    [Google Scholar]
21. Cramer SL, Saha A, Liu J, Tadi S, Tiziani S et al. 2017. Systemic depletion of l-cyst(e)ine with cyst(e)inase increases reactive oxygen species and suppresses tumor growth. Nat. Med. 23:1120–27
    [Google Scholar]
22. Delbridge ARD, Valente LJ, Strasser A 2012. The role of the apoptotic machinery in tumor suppression. Cold Spring Harb. Perspect. Biol. 4:11a008789
    [Google Scholar]
23. Demierre M-F, Higgins PDR, Gruber SB, Hawk E, Lippman SM 2005. Statins and cancer prevention. Nat. Rev. Cancer 5:12930–42
    [Google Scholar]
24. DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C et al. 2011. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475:7354106–9
    [Google Scholar]
25. Diehn M, Cho RW, Lobo NA, Kalisky T, Dorie MJ et al. 2009. Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature 458:7239780–83
    [Google Scholar]
26. Dixon SJ. 2017. Ferroptosis: bug or feature. Immunol. Rev. 277:1150–57
    [Google Scholar]
27. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM et al. 2012. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149:51060–72
    [Google Scholar]
28. Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED et al. 2014. Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis. eLife 3:e02523
    [Google Scholar]
29. Dixon SJ, Winter GE, Musavi LS, Lee ED, Snijder B et al. 2015. Human haploid cell genetics reveals roles for lipid metabolism genes in nonapoptotic cell death. ACS Chem. Biol. 10:71604–9
    [Google Scholar]
30. Doll S, Proneth B, Tyurina YY, Panzilius E, Kobayashi S et al. 2017. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition. Nat. Chem. Biol. 13:191–98
    [Google Scholar]
31. Dolma S, Lessnick SL, Hahn WC, Stockwell BR 2003. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3:3285–96
    [Google Scholar]
32. Evan GI, Vousden KH 2001. Proliferation, cell cycle and apoptosis in cancer. Nature 411:6835342–48
    [Google Scholar]
33. Friedmann Angeli JP, Schneider M, Proneth B, Tyurina YY, Tyurin VA et al. 2014. Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice. Nat. Cell Biol. 16:121180–91
    [Google Scholar]
34. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D et al. 2018. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25:486–541
    [Google Scholar]
35. Gao M, Jiang X 2017. To eat or not to eat—the metabolic flavor of ferroptosis. Curr. Opin. Cell Biol. 51:58–64
    [Google Scholar]
36. Gao M, Monian P, Pan Q, Zhang W, Xiang J, Jiang X 2016. Ferroptosis is an autophagic cell death process. Cell Res 26:91021–32
    [Google Scholar]
37. Gao M, Monian P, Quadri N, Ramasamy R, Jiang X 2015. Glutaminolysis and transferrin regulate ferroptosis. Mol. Cell 59:2298–308
    [Google Scholar]
38. Gascón S, Murenu E, Masserdotti G, Ortega F, Russo GL et al. 2016. Identification and successful negotiation of a metabolic checkpoint in direct neuronal reprogramming. Cell Stem Cell 18:3396–409
    [Google Scholar]
39. Gaschler MM, Andia AA, Liu H, Csuka JM, Hurlocker B et al. 2018. FINO₂ initiates ferroptosis through GPX4 inactivation and iron oxidation. Nat. Chem. Biol. 14:507–15
    [Google Scholar]
40. Gaschler MM, Stockwell BR 2017. Lipid peroxidation in cell death. Biochem. Biophys. Res. Commun. 482:3419–25
    [Google Scholar]
41. Giampazolias E, Zunino B, Dhayade S, Bock F, Cloix C et al. 2017. Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency. Nat. Cell Biol. 19:91116–29
    [Google Scholar]
42. Gout PW, Buckley AR, Simms CR, Bruchovsky N 2001. Sulfasalazine, a potent suppressor of lymphoma growth by inhibition of the x_c⁻ cystine transporter: a new action for an old drug. Leukemia 15:101633–40
    [Google Scholar]
43. Green DR, Victor B 2012. The pantheon of the fallen: Why are there so many forms of cell death. Trends Cell Biol 22:11555–56
    [Google Scholar]
44. Griffith OW, Meister A 1979. Potent and specific inhibition of glutathione synthesis by buthionine sulfoximine (S-n-butyl homocysteine sulfoximine). J. Biol. Chem. 254:167558–60
    [Google Scholar]
45. Hanahan D, Weinberg RA 2011. Hallmarks of cancer: the next generation. Cell 144:5646–74
    [Google Scholar]
46. Hangauer MJ, Viswanathan VS, Ryan MJ, Bole D, Eaton JK et al. 2017. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition. Nature 551:7679247–50
    [Google Scholar]
47. Harris IS, Treloar AE, Inoue S, Sasaki M, Gorrini C et al. 2015. Glutathione and thioredoxin antioxidant pathways synergize to drive cancer initiation and progression. Cancer Cell 27:2211–22
    [Google Scholar]
48. Hata AN, Niederst MJ, Archibald HL, Gomez-Caraballo M, Siddiqui FM et al. 2016. Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition. Nat. Med. 22:3262–69
    [Google Scholar]
49. Hou W, Xie Y, Song X, Sun X, Lotze MT et al. 2016. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12:81425–28
    [Google Scholar]
50. Inde Z, Dixon SJ 2018. The impact of non-genetic heterogeneity on cancer cell death. Crit. Rev. Biochem. Mol. Biol. 53:199–114
    [Google Scholar]
51. Ingold I, Berndt C, Schmitt S, Doll S, Poschmann G et al. 2018. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis. Cell 172:3409–22
    [Google Scholar]
52. Ishimoto T, Nagano O, Yae T, Tamada M, Motohara T et al. 2011. CD44 variant regulates redox status in cancer cells by stabilizing the xCT subunit of system xc⁻ and thereby promotes tumor growth. Cancer Cell 19:3387–400
    [Google Scholar]
53. Jaramillo MC, Zhang DD 2013. The emerging role of the Nrf2-Keap1 signaling pathway in cancer. Genes Dev 27:202179–91
    [Google Scholar]
54. Jennis M, Kung C-P, Basu S, Budina-Kolomets A, Leu JI-J et al. 2016. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 30:8918–30
    [Google Scholar]
55. Jiang L, Kon N, Li T, Wang S-J, Su T et al. 2015. Ferroptosis as a p53-mediated activity during tumour suppression. Nature 520:754557–62
    [Google Scholar]
56. Johnstone RW, Ruefli AA, Lowe SW 2002. Apoptosis: a link between cancer genetics and chemotherapy. Cell 108:2153–64
    [Google Scholar]
57. Kagan VE, Mao G, Qu F, Angeli JPF, Doll S et al. 2017. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat. Chem. Biol. 13:181–90
    [Google Scholar]
58. Kayagaki N, Stowe IB, Lee BL, O'Rourke K, Anderson K et al. 2015. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature 526:7575666–71
    [Google Scholar]
59. Kerins MJ, Ooi A 2018. The roles of NRF2 in modulating cellular iron homeostasis. Antioxid. Redox Signal. 29:1756–73
    [Google Scholar]
60. Kim SE, Zhang L, Ma K, Riegman M, Chen F et al. 2016. Ultrasmall nanoparticles induce ferroptosis in nutrient-deprived cancer cells and suppress tumour growth. Nat. Nanotechnol. 11:11977–85
    [Google Scholar]
61. Koo G-B, Morgan MJ, Lee D-G, Kim W-J, Yoon J-H et al. 2015. Methylation-dependent loss of RIP3 expression in cancer represses programmed necrosis in response to chemotherapeutics. Cell Res 25:6707–25
    [Google Scholar]
62. Korsmeyer SJ. 1999. BCL-2 gene family and the regulation of programmed cell death. Cancer Res 59:7 Suppl1693s–700s
    [Google Scholar]
63. Kruiswijk F, Labuschagne CF, Vousden KH 2015. p53 in survival, death and metabolic health: a lifeguard with a licence to kill. Nat. Rev. Mol. Cell Biol. 16:7393–405
    [Google Scholar]
64. Lachaier E, Louandre C, Godin C, Saidak Z, Baert M et al. 2014. Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors. Anticancer Res 34:116417–22
    [Google Scholar]
65. Larraufie M-H, Yang WS, Jiang E, Thomas AG, Slusher BS, Stockwell BR 2015. Incorporation of metabolically stable ketones into a small molecule probe to increase potency and water solubility. Bioorg. Med. Chem. Lett. 25:214787–92
    [Google Scholar]
66. Li T, Kon N, Jiang L, Tan M, Ludwig T et al. 2012. Tumor suppression in the absence of p53-mediated cell-cycle arrest, apoptosis, and senescence. Cell 149:61269–83
    [Google Scholar]
67. Lien EC, Lyssiotis CA, Juvekar A, Hu H, Asara JM et al. 2016. Glutathione biosynthesis is a metabolic vulnerability in PI(3)K/Akt-driven breast cancer. Nat. Cell Biol. 18:5572–78
    [Google Scholar]
68. Linkermann A, Skouta R, Himmerkus N, Mulay SR, Dewitz C et al. 2014. Synchronized renal tubular cell death involves ferroptosis. PNAS 111:4716836–41
    [Google Scholar]
69. Liu DS, Duong CP, Haupt S, Montgomery KG, House CM et al. 2017. Inhibiting the system x_C⁻/glutathione axis selectively targets cancers with mutant-p53 accumulation. Nat Commun 8:14844
    [Google Scholar]
70. Louandre C, Ezzoukhry Z, Godin C, Barbare J-C, Mazière J-C et al. 2013. Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib. Int. J. Cancer 133:71732–42
    [Google Scholar]
71. Maddocks ODK, Berkers CR, Mason SM, Zheng L, Blyth K et al. 2013. Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature 493:7433542–46
    [Google Scholar]
72. Magtanong L, Ko PJ, Dixon SJ 2016. Emerging roles for lipids in non-apoptotic cell death. Cell Death Differ 23:1099–109
    [Google Scholar]
73. Mai TT, Hamaï A, Hienzsch A, Cañeque T, Müller S et al. 2017. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat. Chem. 9:101025–33
    [Google Scholar]
74. Mancias JD, Wang X, Gygi SP, Harper JW, Kimmelman AC 2014. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 509:7498105–9
    [Google Scholar]
75. Moosmann B, Behl C 2004. Selenoprotein synthesis and side-effects of statins. Lancet 363:9412892–94
    [Google Scholar]
76. Ni Chonghaile T, Sarosiek KA, Vo T-T, Ryan JA, Tammareddi A et al. 2011. Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy. Science 334:60591129–33
    [Google Scholar]
77. Poursaitidis I, Wang X, Crighton T, Labuschagne C, Mason D et al. 2017. Oncogene-selective sensitivity to synchronous cell death following modulation of the amino acid nutrient cystine. Cell Rep 18:112547–56
    [Google Scholar]
78. Qi X-F, Kim D-H, Yoon Y-S, Kim S-K, Cai D-Q et al. 2010. Involvement of oxidative stress in simvastatin-induced apoptosis of murine CT26 colon carcinoma cells. Toxicol. Lett. 199:3277–87
    [Google Scholar]
79. Robe PA, Martin DH, Nguyen-Khac MT, Artesi M, Deprez M et al. 2009. Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of sulfasalazine for the treatment of progressing malignant gliomas in adults. BMC Cancer 9:1372
    [Google Scholar]
80. Roh J-L, Kim EH, Jang H, Shin D 2017. Nrf2 inhibition reverses the resistance of cisplatin-resistant head and neck cancer cells to artesunate-induced ferroptosis. Redox Biol 11:254–62
    [Google Scholar]
81. Romero R, Sayin VI, Davidson SM, Bauer MR, Singh SX et al. 2017. Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nat. Med. 23:111362–68
    [Google Scholar]
82. Sarosiek KA, Fraser C, Muthalagu N, Bhola PD, Chang W et al. 2017. Developmental regulation of mitochondrial apoptosis by c-Myc governs age- and tissue-specific sensitivity to cancer therapeutics. Cancer Cell 31:1142–56
    [Google Scholar]
83. Sarosiek KA, Ni Chonghaile T, Letai A 2013. Mitochondria: gatekeepers of response to chemotherapy. Trends Cell Biol 23:12612–19
    [Google Scholar]
84. Sato H, Shiiya A, Kimata M, Maebara K, Tamba M et al. 2005. Redox imbalance in cystine/glutamate transporter-deficient mice. J. Biol. Chem. 280:4537423–29
    [Google Scholar]
85. Sato H, Tamba M, Ishii T, Bannai S 1999. Cloning and expression of a plasma membrane cystine/glutamate exchange transporter composed of two distinct proteins. J. Biol. Chem. 274:1711455–58
    [Google Scholar]
86. Schoenfeld JD, Sibenaller ZA, Mapuskar KA, Wagner BA, Cramer-Morales KL et al. 2017. O₂^·− and H₂O₂-mediated disruption of Fe metabolism causes the differential susceptibility of NSCLC and GBM cancer cells to pharmacological ascorbate. Cancer Cell 31:4487–88
    [Google Scholar]
87. Schonberg DL, Miller TE, Wu Q, Flavahan WA, Das NK et al. 2015. Preferential iron trafficking characterizes glioblastoma stem-like cells. Cancer Cell 28:4441–55
    [Google Scholar]
88. Schott C, Graab U, Cuvelier N, Hahn H, Fulda S 2015. Oncogenic RAS mutants confer resistance of RMS13 rhabdomyosarcoma cells to oxidative stress-induced ferroptotic cell death. Front. Oncol. 5:131
    [Google Scholar]
89. Seiler A, Schneider M, Förster H, Roth S, Wirth EK et al. 2008. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 8:3237–48
    [Google Scholar]
90. Sharma SV, Lee DY, Li B, Quinlan MP, Takahashi F et al. 2010. A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations. Cell 141:169–80
    [Google Scholar]
91. Shimada K, Hayano M, Pagano NC, Stockwell BR 2016.a Cell-line selectivity improves the predictive power of pharmacogenomic analyses and helps identify NADPH as biomarker for ferroptosis sensitivity. Cell Chem. Biol. 23:2225–35
    [Google Scholar]
92. Shimada K, Skouta R, Kaplan A, Yang WS, Hayano M et al. 2016.b Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis. Nat. Chem. Biol. 12:7497–503
    [Google Scholar]
93. Shitara K, Doi T, Nagano O, Imamura CK, Ozeki T et al. 2017. Dose-escalation study for the targeting of CD44v⁺ cancer stem cells by sulfasalazine in patients with advanced gastric cancer (EPOC1205). Gastric Cancer 20:2341–49
    [Google Scholar]
94. Singh A, Venkannagari S, Oh KH, Zhang Y-Q, Rohde JM et al. 2016. Small molecule inhibitor of NRF2 selectively intervenes therapeutic resistance in KEAP1-deficient NSCLC tumors. ACS Chem. Biol. 11:113214–25
    [Google Scholar]
95. Skouta R, Dixon SJ, Wang J, Dunn DE, Orman M et al. 2014. Ferrostatins inhibit oxidative lipid damage and cell death in diverse disease models. J. Am. Chem. Soc. 136:124551–56
    [Google Scholar]
96. Somfai-Relle S, Suzukake K, Vistica BP, Vistica DT 1984. Reduction in cellular glutathione by buthionine sulfoximine and sensitization of murine tumor cells resistant to l-phenylalanine mustard. Biochem. Pharmacol. 33:3485–90
    [Google Scholar]
97. Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M et al. 2017. Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 171:2273–85
    [Google Scholar]
98. Sun X, Ou Z, Chen R, Niu X, Chen D et al. 2016. Activation of the p62-Keap1-NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology 63:1173–84
    [Google Scholar]
99. Tarangelo A, Magtanong L, Bieging-Rolett KT, Li Y, Ye J et al. 2018. p53 suppresses metabolic stress-induced ferroptosis in cancer cells. Cell Rep 22:3569–75
    [Google Scholar]
100. Timmerman LA, Holton T, Yuneva M, Louie RJ, Padró M et al. 2013. Glutamine sensitivity analysis identifies the xCT antiporter as a common triple-negative breast tumor therapeutic target. Cancer Cell 24:4450–65
     [Google Scholar]
101. Torii S, Shintoku R, Kubota C, Yaegashi M, Torii R et al. 2016. An essential role for functional lysosomes in ferroptosis of cancer cells. Biochem. J. 473:6769–77
     [Google Scholar]
102. Torti SV, Torti FM 2013. Iron and cancer: more ore to be mined. Nat. Rev. Cancer 13:5342–55
     [Google Scholar]
103. Tsoi J, Robert L, Paraiso K, Galvan C, Sheu KM et al. 2018. Multi-stage differentiation defines melanoma subtypes with differential vulnerability to drug-induced iron-dependent oxidative stress. Cancer Cell 33:5890–904
     [Google Scholar]
104. Ursini F, Maiorino M, Gregolin C 1985. The selenoenzyme phospholipid hydroperoxide glutathione peroxidase. Biochim. Biophys. Acta 839:162–70
     [Google Scholar]
105. Villablanca JG, Volchenboum SL, Cho H, Kang MH, Cohn SL et al. 2016. A phase I new approaches to neuroblastoma therapy study of buthionine sulfoximine and melphalan with autologous stem cells for recurrent/refractory high-risk neuroblastoma. Pediatr. Blood Cancer 63:81349–56
     [Google Scholar]
106. Viswanathan VS, Ryan MJ, Dhruv HD, Gill S, Eichhoff OM et al. 2017. Dependency of a therapy-resistant state of cancer cells on a lipid peroxidase pathway. Nature 547:7664453–57
     [Google Scholar]
107. Wakabayashi N, Itoh K, Wakabayashi J, Motohashi H, Noda S et al. 2003. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat. Genet. 35:3238–45
     [Google Scholar]
108. Wang GX, Tu H-C, Dong Y, Skanderup AJ, Wang Y et al. 2017. ΔNp63 inhibits oxidative stress-induced cell death, including ferroptosis, and cooperates with the BCL-2 family to promote clonogenic survival. Cell Rep 21:102926–39
     [Google Scholar]
109. Wang S-J, Li D, Ou Y, Jiang L, Chen Y et al. 2016. Acetylation is crucial for p53-mediated ferroptosis and tumor suppression. Cell Rep 17:2366–73
     [Google Scholar]
110. Wang Y, Gao W, Shi X, Ding J, Liu W et al. 2017. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature 547:766199–103
     [Google Scholar]
111. Warner GJ, Berry MJ, Moustafa ME, Carlson BA, Hatfield DL, Faust JR 2000. Inhibition of selenoprotein synthesis by selenocysteine tRNA^[Ser]Sec lacking isopentenyladenosine. J. Biol. Chem. 275:3628110–19
     [Google Scholar]
112. Weiwer M, Bittker J, Lewis TA, Shimada K, Yang WS et al. 2012. Development of small-molecule probes that selectively kill cells induced to express mutant RAS. Bioorg. Med. Chem. Lett. 22:41822–26
     [Google Scholar]
113. Wenzel SE, Tyurina YY, Zhao J, St. Croix CM, Dar HH et al. 2017. PEBP1 wardens ferroptosis by enabling lipoxygenase generation of lipid death signals. Cell 171:3628–41.e26
     [Google Scholar]
114. Woo JH, Shimoni Y, Yang WS, Subramaniam P, Iyer A et al. 2015. Elucidating compound mechanism of action by network perturbation analysis. Cell 162:2441–51
     [Google Scholar]
115. Xie Y, Zhu S, Song X, Sun X, Fan Y et al. 2017. The tumor suppressor p53 limits ferroptosis by blocking DPP4 activity. Cell Rep 20:71692–704
     [Google Scholar]
116. Yagoda N, von Rechenberg M, Zaganjor E, Bauer AJ, Yang WS et al. 2007. RAS–RAF–MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447:7146864–68
     [Google Scholar]
117. Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR 2016. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. PNAS 113:34E4966–75
     [Google Scholar]
118. Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R et al. 2014. Regulation of ferroptotic cancer cell death by GPX4. Cell 156:1–2317–31
     [Google Scholar]
119. Yang WS, Stockwell BR 2008. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem. Biol. 15:3234–45
     [Google Scholar]
120. Yang WS, Stockwell BR 2016. Ferroptosis: death by lipid peroxidation. Trends Cell Biol 26:3165–76
     [Google Scholar]
121. Yuan H, Li X, Zhang X, Kang R, Tang D 2016.a CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation. Biochem. Biophys. Res. Commun. 478:2838–44
     [Google Scholar]
122. Yuan H, Li X, Zhang X, Kang R, Tang D 2016.b Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem. Biophys. Res. Commun. 478:31338–43
     [Google Scholar]
123. Yun J, Mullarky E, Lu C, Bosch KN, Kavalier A et al. 2015. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science 350:62661391–96
     [Google Scholar]
124. Zilka O, Shah R, Li B, Friedmann Angeli JP, Griesser M et al. 2017. On the mechanism of cytoprotection by ferrostatin-1 and liproxstatin-1 and the role of lipid peroxidation in ferroptotic cell death. ACS Cent. Sci. 3:3232–43
     [Google Scholar]