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Current Molecular Medicine

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ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

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Review Article

Emerging Role of Ferroptosis in Breast Cancer: Characteristics, Therapy, and Translational Implications for the Present and Future

In Press, (this is not the final "Version of Record"). Available online 17 October, 2023
Author(s): Suman Kumar Ray and Sukhes Mukherjee*
Published on: 17 October, 2023

DOI: 10.2174/1566524023666230913105735

Price: $95

Abstract

Ferroptosis is a nonapoptotic, iron-dependent form of cell death that can be actuated in disease cells by expected improvements and manufactured specialists. Different studies have recently resurrected the role of this newly discovered cell death pathway and demonstrated its efficacy in treating breast cancer. Breast cancer is the most well-known type of cancer among women worldwide. Despite many years of research focusing on cell death in breast cancer, counting apoptosis, clinical treatment leftovers are difficult due to the high likelihood of recurrence. Ferroptosis is defined by a lack of lipid peroxide repair capacity by phospholipid hydroperoxides GPX4, accessibility of redox-active iron, and followed oxidation of polyunsaturated fatty acids acid-containing phospholipids signalling, amino acid and iron metabolism, ferritinophagy, epithelial-tomesenchymal transition, cell adhesion, and mevalonate and phospholipid biosynthesis can all be factors that influence ferroptosis susceptibility. Ferroptosis, an iron-dependent controlled cell death caused by excessive lipid peroxidation, has been entwined in breast cancer development and therapeutic response for the past decade. Advances in enhancing clinical drugs targeting ferroptosis are developing silver linings to treat breast cancer. Ferroptosis is influenced by metabolism and the expression of certain genes, making it a prospective therapeutic target for monitoring malignant growth and an appealing target for precision cancer medication disclosure. In the coming years, research into biomarkers to follow ferroptosis in patients with breast cancer and the course of events and the subsequent use of novel ferroptosis-based treatments will be captious. We present a fundamental analysis of the actual understanding of molecular mechanisms along with regulatory networks associated with ferroptosis, expected physiological functions in growth concealment, ferroptosis-associated differentially expressed genes, treatment targeting potential, and recent advances in the development of therapeutic strategies in this review.

[1]
Li Z, Chen L, Chen C, et al. Targeting ferroptosis in breast cancer. Biomark Res 2020; 8(1): 58.
[http://dx.doi.org/10.1186/s40364-020-00230-3] [PMID: 33292585]
[2]
Urooj T, Wasim B, Mushtaq S, Shah SNN, Shah M. Cancer cell-derived secretory factors in breast cancer-associated lung metastasis: Their mechanism and future prospects. Curr Cancer Drug Targets 2020; 20(3): 168-86.
[http://dx.doi.org/10.2174/1568009620666191220151856] [PMID: 31858911]
[3]
DeSantis CE, Ma J, Gaudet MM, et al. Breast cancer statistics, 2019. CA Cancer J Clin 2019; 69(6): 438-51.
[http://dx.doi.org/10.3322/caac.21583] [PMID: 31577379]
[4]
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68(6): 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[5]
Zhang Y, Wang Y, Tian G, Jiang T. Long non-coding RNA-based signatures to improve prognostic prediction of breast cancer. Medicine 2020; 99(40): e22203.
[http://dx.doi.org/10.1097/MD.0000000000022203] [PMID: 33019395]
[6]
Liu B, Fan Y, Song Z, et al. Identification of DRP1 as a prognostic factor correlated with immune infiltration in breast cancer. Int Immunopharmacol 2020; 89(Pt B): 107078.
[http://dx.doi.org/10.1016/j.intimp.2020.107078] [PMID: 33049497]
[7]
Waks AG, Winer EP. Breast cancer treatment. JAMA 2019; 321(3): 288-300.
[http://dx.doi.org/10.1001/jama.2018.19323] [PMID: 30667505]
[8]
Holohan C, Van Schaeybroeck S, Longley DB, Johnston PG. Cancer drug resistance: An evolving paradigm. Nat Rev Cancer 2013; 13(10): 714-26.
[http://dx.doi.org/10.1038/nrc3599] [PMID: 24060863]
[9]
Dixon SJ, Stockwell BR. The hallmarks of ferroptosis. Annu Rev Cancer Biol 2019; 3(1): 35-54.
[http://dx.doi.org/10.1146/annurev-cancerbio-030518-055844]
[10]
Fearnhead HO, Vandenabeele P, Vanden Berghe T. How do we fit ferroptosis in the family of regulated cell death? Cell Death Differ 2017; 24(12): 1991-8.
[http://dx.doi.org/10.1038/cdd.2017.149] [PMID: 28984871]
[11]
Xie Y, Hou W, Song X, et al. Ferroptosis: Process and function. Cell Death Differ 2016; 23(3): 369-79.
[http://dx.doi.org/10.1038/cdd.2015.158] [PMID: 26794443]
[12]
Wang W, Green M, Choi JE, et al. CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy. Nature 2019; 569(7755): 270-4.
[http://dx.doi.org/10.1038/s41586-019-1170-y] [PMID: 31043744]
[13]
Wu J, Minikes AM, Gao M, et al. Intercellular interaction dictates cancer cell ferroptosis via NF2–YAP signalling. Nature 2019; 572(7769): 402-6.
[http://dx.doi.org/10.1038/s41586-019-1426-6] [PMID: 31341276]
[14]
Manz DH, Blanchette NL, Paul BT, Torti FM, Torti SV. Iron and cancer: Recent insights. Ann N Y Acad Sci 2016; 1368(1): 149-61.
[http://dx.doi.org/10.1111/nyas.13008] [PMID: 26890363]
[15]
Xu X, Chen Y, Zhang Y, Yao Y, Ji P. Highly stable and biocompatible hyaluronic acid-rehabilitated nanoscale MOF-Fe 2+ induced ferroptosis in breast cancer cells. J Mater Chem B Mater Biol Med 2020; 8(39): 9129-38.
[http://dx.doi.org/10.1039/D0TB01616K]
[16]
Brown CW, Amante JJ, Chhoy P, et al. Prominin2 drives ferroptosis resistance by stimulating iron export. Dev Cell 2019; 51(5): 575-586.e4.
[http://dx.doi.org/10.1016/j.devcel.2019.10.007] [PMID: 31735663]
[17]
Mou Y, Wang J, Wu J, et al. Ferroptosis, a new form of cell death: Opportunities and challenges in cancer. J Hematol Oncol 2019; 12(1): 34.
[http://dx.doi.org/10.1186/s13045-019-0720-y] [PMID: 30925886]
[18]
Dolma S, Lessnick SL, Hahn WC, Stockwell BR. Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 2003; 3(3): 285-96.
[http://dx.doi.org/10.1016/S1535-6108(03)00050-3] [PMID: 12676586]
[19]
Dixon SJ, Lemberg KM, Lamprecht MR, et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell 2012; 149(5): 1060-72.
[http://dx.doi.org/10.1016/j.cell.2012.03.042] [PMID: 22632970]
[20]
Galluzzi L, Vitale I, Aaronson SA, et al. Molecular mechanisms of cell death: Recommendations of the nomenclature committee on cell death 2018. Cell Death Differ 2018; 25(3): 486-541.
[http://dx.doi.org/10.1038/s41418-017-0012-4] [PMID: 29362479]
[21]
Conrad M, Kagan VE, Bayir H, et al. Regulation of lipid peroxidation and ferroptosis in diverse species. Genes Dev 2018; 32(9-10): 602-19.
[http://dx.doi.org/10.1101/gad.314674.118] [PMID: 29802123]
[22]
Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Res 2019; 29(5): 347-64.
[http://dx.doi.org/10.1038/s41422-019-0164-5] [PMID: 30948788]
[23]
Yu H, Guo P, Xie X, Wang Y, Chen G. Ferroptosis, a new form of cell death, and its relationships with tumourous diseases. J Cell Mol Med 2017; 21(4): 648-57.
[http://dx.doi.org/10.1111/jcmm.13008] [PMID: 27860262]
[24]
Hassannia B, Vandenabeele P, Vanden Berghe T. Targeting ferroptosis to iron out cancer. Cancer Cell 2019; 35(6): 830-49.
[http://dx.doi.org/10.1016/j.ccell.2019.04.002] [PMID: 31105042]
[25]
Wang YY, Liu XL, Zhao R. Induction of pyroptosis and its implications in cancer management. Front Oncol 2019; 9: 971.
[http://dx.doi.org/10.3389/fonc.2019.00971] [PMID: 31616642]
[26]
Yang WS, Stockwell BR. Ferroptosis: Death by lipid peroxidation. Trends Cell Biol 2016; 26(3): 165-76.
[http://dx.doi.org/10.1016/j.tcb.2015.10.014] [PMID: 26653790]
[27]
Hangauer MJ, Viswanathan VS, Ryan MJ, et al. Drug-tolerant persister cancer cells are vulnerable to GPX4 inhibition. Nature 2017; 551(7679): 247-50.
[http://dx.doi.org/10.1038/nature24297] [PMID: 29088702]
[28]
Bobiński R, Dutka M, Pizon M, Waksmańska W, Pielesz A. Ferroptosis, acyl starvation, and breast cancer. Mol Pharmacol 2023; 103(3): 132-44.
[http://dx.doi.org/10.1124/molpharm.122.000607] [PMID: 36750321]
[29]
Wang Z, Wang M, Carr BI. Involvement of receptor tyrosine phosphatase DEP-1 mediated PI3K-cofilin signaling pathway in Sorafenib-induced cytoskeletal rearrangement in hepatoma cells. J Cell Physiol 2010; 224(2): 559-65.
[http://dx.doi.org/10.1002/jcp.22160] [PMID: 20432459]
[30]
Ždralević M, Vučetić M, Daher B, Marchiq I, Parks SK, Pouysségur J. Disrupting the ‘Warburg effect’ re-routes cancer cells to OXPHOS offering a vulnerability point via ‘ferroptosis’-induced cell death. Adv Biol Regul 2018; 68: 55-63.
[http://dx.doi.org/10.1016/j.jbior.2017.12.002] [PMID: 29306548]
[31]
Huang J, Chen S, Hu L, et al. Mitoferrin-1 is involved in the progression of alzheimer’s disease through targeting mitochondrial iron metabolism in a caenorhabditis elegans model of alzheimer’s disease. Neuroscience 2018; 385: 90-101.
[http://dx.doi.org/10.1016/j.neuroscience.2018.06.011] [PMID: 29908215]
[32]
Strzyz P. Iron expulsion by exosomes drives ferroptosis resistance. Nat Rev Mol Cell Biol 2020; 21(1): 4-5.
[http://dx.doi.org/10.1038/s41580-019-0195-2] [PMID: 31748716]
[33]
Wang YQ, Chang SY, Wu Q, et al. The protective role of mitochondrial ferritin on erastin-induced ferroptosis. Front Aging Neurosci 2016; 8: 308.
[http://dx.doi.org/10.3389/fnagi.2016.00308] [PMID: 28066232]
[34]
Battaglia AM, Chirillo R, Aversa I, Sacco A, Costanzo F, Biamonte F. Ferroptosis and cancer: Mitochondria meet the “Iron Maiden” cell death. Cells 2020; 9(6): 1505.
[http://dx.doi.org/10.3390/cells9061505] [PMID: 32575749]
[35]
Kagan VE, Mao G, Qu F, et al. Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis. Nat Chem Biol 2017; 13(1): 81-90.
[http://dx.doi.org/10.1038/nchembio.2238] [PMID: 27842066]
[36]
Yuan H, Li X, Zhang X, Kang R, Tang D. Identification of ACSL4 as a biomarker and contributor of ferroptosis. Biochem Biophys Res Commun 2016; 478(3): 1338-43.
[http://dx.doi.org/10.1016/j.bbrc.2016.08.124] [PMID: 27565726]
[37]
Agmon E, Solon J, Bassereau P, Stockwell BR. Modeling the effects of lipid peroxidation during ferroptosis on membrane properties. Sci Rep 2018; 8(1): 5155.
[http://dx.doi.org/10.1038/s41598-018-23408-0] [PMID: 29581451]
[38]
Mancias JD, Wang X, Gygi SP, Harper JW, Kimmelman AC. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 2014; 509(7498): 105-9.
[http://dx.doi.org/10.1038/nature13148] [PMID: 24695223]
[39]
Alvarez SW, Sviderskiy VO, Terzi EM, et al. NFS1 undergoes positive selection in lung tumours and protects cells from ferroptosis. Nature 2017; 551(7682): 639-43.
[http://dx.doi.org/10.1038/nature24637] [PMID: 29168506]
[40]
Yuan H, Li X, Zhang X, Kang R, Tang D. CISD1 inhibits ferroptosis by protection against mitochondrial lipid peroxidation. Biochem Biophys Res Commun 2016; 478(2): 838-44.
[http://dx.doi.org/10.1016/j.bbrc.2016.08.034] [PMID: 27510639]
[41]
Ingold I, Berndt C, Schmitt S, et al. Selenium utilization by GPX4 is required to prevent hydroperoxide-induced ferroptosis. Cell 2018; 172(3): 409-422.e21.
[http://dx.doi.org/10.1016/j.cell.2017.11.048] [PMID: 29290465]
[42]
Seiler A, Schneider M, Förster H, et al. Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-mediated cell death. Cell Metab 2008; 8(3): 237-48.
[http://dx.doi.org/10.1016/j.cmet.2008.07.005] [PMID: 18762024]
[43]
Yang WS, SriRamaratnam R, Welsch ME, et al. Regulation of ferroptotic cancer cell death by GPX4. Cell 2014; 156(1-2): 317-31.
[http://dx.doi.org/10.1016/j.cell.2013.12.010] [PMID: 24439385]
[44]
Ray SK, Mukherjee S. Epigenetic reprogramming and landscape of transcriptomic interactions: Impending therapeutic interference of triple-negative breast cancer in molecular medicine. Curr Mol Med 2022; 22(10): 835-50.
[http://dx.doi.org/10.2174/1566524021666211206092437] [PMID: 34872474]
[45]
Ray SK, Mukherjee S. Consequences of extracellular matrix remodeling in headway and metastasis of cancer along with novel immunotherapies: A great promise for future endeavor. Anticancer Agents Med Chem 2022; 22(7): 1257-71.
[http://dx.doi.org/10.2174/1871520621666210712090017] [PMID: 34254930]
[46]
Wang H, Cheng Y, Mao C, et al. Emerging mechanisms and targeted therapy of ferroptosis in cancer. Mol Ther 2021; 29(7): 2185-208.
[http://dx.doi.org/10.1016/j.ymthe.2021.03.022] [PMID: 33794363]
[47]
Bartsch H, Nair J, Owen RW. Dietary polyunsaturated fatty acids and cancers of the breast and colorectum: emerging evidence for their role as risk modifiers. Carcinogenesis 1999; 20(12): 2209-18.
[http://dx.doi.org/10.1093/carcin/20.12.2209] [PMID: 10590211]
[48]
Zanoaga O, Jurj A, Raduly L, et al. Implications of dietary ω-3 and ω-6 polyunsaturated fatty acids in breast cancer. Exp Ther Med 2018; 15(2): 1167-76.
[PMID: 29434704]
[49]
Chajès V, Torres-Mejía G, Biessy C, et al. ω-3 and ω-6 Polyunsaturated fatty acid intakes and the risk of breast cancer in Mexican women: Impact of obesity status. Cancer Epidemiol Biomarkers Prev 2012; 21(2): 319-26.
[http://dx.doi.org/10.1158/1055-9965.EPI-11-0896] [PMID: 22194528]
[50]
Murff HJ, Shu XO, Li H, et al. Dietary polyunsaturated fatty acids and breast cancer risk in Chinese women: A prospective cohort study. Int J Cancer 2011; 128(6): 1434-41.
[http://dx.doi.org/10.1002/ijc.25703] [PMID: 20878979]
[51]
Thiébaut ACM, Chajès V, Gerber M, et al. Dietary intakes of ω-6 and ω-3 polyunsaturated fatty acids and the risk of breast cancer. Int J Cancer 2009; 124(4): 924-31.
[http://dx.doi.org/10.1002/ijc.23980] [PMID: 19035453]
[52]
Yang B, Ren XL, Fu YQ, Gao JL, Li D. Ratio of n-3/n-6 PUFAs and risk of breast cancer: A meta-analysis of 274135 adult females from 11 independent prospective studies. BMC Cancer 2014; 14(1): 105.
[http://dx.doi.org/10.1186/1471-2407-14-105] [PMID: 24548731]
[53]
Dodson M, Castro-Portuguez R, Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol 2019; 23: 101107.
[http://dx.doi.org/10.1016/j.redox.2019.101107] [PMID: 30692038]
[54]
Sun X, Ou Z, Chen R, et al. Activation of the p62‐Keap1‐NRF2 pathway protects against ferroptosis in hepatocellular carcinoma cells. Hepatology 2016; 63(1): 173-84.
[http://dx.doi.org/10.1002/hep.28251] [PMID: 26403645]
[55]
Rojo de la Vega M, Chapman E, Zhang DD. NRF2 and the hallmarks of cancer. Cancer Cell 2018; 34(1): 21-43.
[http://dx.doi.org/10.1016/j.ccell.2018.03.022] [PMID: 29731393]
[56]
Zhou XL, Zhu CY, Wu ZG, Guo X, Zou W. The oncoprotein HBXIP competitively binds KEAP1 to activate NRF2 and enhance breast cancer cell growth and metastasis. Oncogene 2019; 38(21): 4028-46.
[http://dx.doi.org/10.1038/s41388-019-0698-5] [PMID: 30692632]
[57]
Udler M, Maia AT, Cebrian A, et al. Common germline genetic variation in antioxidant defense genes and survival after diagnosis of breast cancer. J Clin Oncol 2007; 25(21): 3015-23.
[http://dx.doi.org/10.1200/JCO.2006.10.0099] [PMID: 17634480]
[58]
Lee S-H. Insulin-induced GPX4 expression in breast cancer cells. J Soonchunhyang Med Sci 2008; 14(2): 27-32.
[59]
Monaco ME, Creighton CJ, Lee P, Zou X, Topham MK, Stafforini DM. Expression of long-chain fatty Acyl-CoA synthetase 4 in breast and prostate cancers is associated with sex steroid hormone receptor negativity. Transl Oncol 2010; 3(2): 91-8.
[http://dx.doi.org/10.1593/tlo.09202] [PMID: 20360933]
[60]
Wu X, Li Y, Wang J, et al. Long chain fatty Acyl-CoA synthetase 4 is a biomarker for and mediator of hormone resistance in human breast cancer. PLoS One 2013; 8(10): e77060.
[http://dx.doi.org/10.1371/journal.pone.0077060] [PMID: 24155918]
[61]
Chu B, Kon N, Chen D, et al. ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway. Nat Cell Biol 2019; 21(5): 579-91.
[http://dx.doi.org/10.1038/s41556-019-0305-6] [PMID: 30962574]
[62]
Ou Y, Wang SJ, Li D, Chu B, Gu W. Activation of SAT1 engages polyamine metabolism with p53-mediated ferroptotic responses. Proc Natl Acad Sci 2016; 113(44): E6806-12.
[http://dx.doi.org/10.1073/pnas.1607152113] [PMID: 27698118]
[63]
Gasco M, Shami S, Crook T. The p53 pathway in breast cancer. Breast Cancer Res 2002; 4(2): 70-6.
[http://dx.doi.org/10.1186/bcr426] [PMID: 11879567]
[64]
Bieging KT, Mello SS, Attardi LD. Unravelling mechanisms of p53-mediated tumour suppression. Nat Rev Cancer 2014; 14(5): 359-70.
[http://dx.doi.org/10.1038/nrc3711] [PMID: 24739573]
[65]
Tarangelo A, Magtanong L, Bieging-Rolett KT, et al. p53 Suppresses metabolic stress-induced ferroptosis in cancer cells. Cell Rep 2018; 22(3): 569-75.
[http://dx.doi.org/10.1016/j.celrep.2017.12.077] [PMID: 29346757]
[66]
Liu XX, Li XJ, Zhang B, et al. MicroRNA-26b is underexpressed in human breast cancer and induces cell apoptosis by targeting SLC7A11. FEBS Lett 2011; 585(9): 1363-7.
[http://dx.doi.org/10.1016/j.febslet.2011.04.018] [PMID: 21510944]
[67]
Sato R, Nakano T, Hosonaga M, et al. RNA sequencing analysis reveals interactions between breast cancer or melanoma cells and the tissue microenvironment during brain metastasis. BioMed Res Int 2017; 2017: 1-10.
[http://dx.doi.org/10.1155/2017/8032910] [PMID: 28210624]
[68]
Chen MS, Wang SF, Hsu CY, et al. CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2α-ATF4 pathway. Oncotarget 2017; 8(70): 114588-602.
[http://dx.doi.org/10.18632/oncotarget.23055] [PMID: 29383104]
[69]
Yang WS, Stockwell BR. Synthetic lethal screening identifies compounds activating iron-dependent, nonapoptotic cell death in oncogenic-RAS-harboring cancer cells. Chem Biol 2008; 15(3): 234-45.
[http://dx.doi.org/10.1016/j.chembiol.2008.02.010] [PMID: 18355723]
[70]
Poursaitidis I, Wang X, Crighton T, et al. Oncogene–selective sensitivity to synchronous cell death following modulation of the amino acid nutrient cystine. Cell Rep 2017; 18(11): 2547-56.
[http://dx.doi.org/10.1016/j.celrep.2017.02.054] [PMID: 28297659]
[71]
Hole PS, Pearn L, Tonks AJ, et al. Ras-induced reactive oxygen species promote growth factor–independent proliferation in human CD34+ hematopoietic progenitor cells. Blood 2010; 115(6): 1238-46.
[http://dx.doi.org/10.1182/blood-2009-06-222869] [PMID: 20007804]
[72]
Nguyen T, Nioi P, Pickett CB. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J Biol Chem 2009; 284(20): 13291-5.
[http://dx.doi.org/10.1074/jbc.R900010200] [PMID: 19182219]
[73]
DeNicola GM, Karreth FA, Humpton TJ, et al. Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 2011; 475(7354): 106-9.
[http://dx.doi.org/10.1038/nature10189] [PMID: 21734707]
[74]
Pietsch EC, Chan JY, Torti FM, Torti SV. Nrf2 mediates the induction of ferritin H in response to xenobiotics and cancer chemopreventive dithiolethiones. J Biol Chem 2003; 278(4): 2361-9.
[http://dx.doi.org/10.1074/jbc.M210664200] [PMID: 12435735]
[75]
Hou W, Xie Y, Song X, et al. Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 2016; 12(8): 1425-8.
[http://dx.doi.org/10.1080/15548627.2016.1187366] [PMID: 27245739]
[76]
Yang M, Chen P, Liu J. Clockophagy is a novel selective autophagy process favoring ferroptosis. Sci Adv 2019; 5(7): 2238.
[http://dx.doi.org/10.1126/sciadv.aaw2238]
[77]
Liu J, Yang M, Kang R, Klionsky DJ, Tang D. Autophagic degradation of the circadian clock regulator promotes ferroptosis. Autophagy 2019; 15(11): 2033-5.
[http://dx.doi.org/10.1080/15548627.2019.1659623] [PMID: 31441366]
[78]
Song X, Zhu S, Chen P, et al. AMPK-mediated BECN1 phosphorylation promotes ferroptosis by directly blocking system Xc(-) activity. Curr Biol 2018; 28(15): 2388-2399.e5.
[http://dx.doi.org/10.1016/j.cub.2018.05.094] [PMID: 30057310]
[79]
Anandhan A, Dodson M, Schmidlin CJ, Liu P, Zhang DD. Breakdown of an ironclad defense system: The critical role of NRF2 in mediating ferroptosis. Cell Chem Biol 2020; 27(4): 436-47.
[http://dx.doi.org/10.1016/j.chembiol.2020.03.011] [PMID: 32275864]
[80]
Andrews NC, Schmidt PJ. Iron homeostasis. Annu Rev Physiol 2007; 69(1): 69-85.
[http://dx.doi.org/10.1146/annurev.physiol.69.031905.164337] [PMID: 17014365]
[81]
Fujihara KM, Zhang BZ, Clemons NJ. Opportunities for Ferroptosis in Cancer Therapy. Antioxidants 2021; 10(6): 986.
[http://dx.doi.org/10.3390/antiox10060986] [PMID: 34205617]
[82]
Ward DM, Kaplan J. Ferroportin-mediated iron transport: Expression and regulation. Biochim Biophys Acta Mol Cell Res 2012; 1823(9): 1426-33.
[http://dx.doi.org/10.1016/j.bbamcr.2012.03.004] [PMID: 22440327]
[83]
Chen PH, Wu J, Ding CC, et al. Kinome screen of ferroptosis reveals a novel role of ATM in regulating iron metabolism. Cell Death Differ 2020; 27(3): 1008-22.
[http://dx.doi.org/10.1038/s41418-019-0393-7] [PMID: 31320750]
[84]
Geng N, Shi BJ, Li SL, et al. Knockdown of ferroportin accelerates erastin-induced ferroptosis in neuroblastoma cells. Eur Rev Med Pharmacol Sci 2018; 22(12): 3826-36.
[http://dx.doi.org/10.26355/eurrev_201806_15267] [PMID: 29949159]
[85]
Shi ZZ, Fan ZW, Chen YX, et al. Ferroptosis in carcinoma: Regulatory mechanisms and new method for cancer therapy. OncoTargets Ther 2019; 12: 11291-304.
[http://dx.doi.org/10.2147/OTT.S232852] [PMID: 31908494]
[86]
Doll S, Freitas FP, Shah R, et al. FSP1 is a glutathione-independent ferroptosis suppressor. Nature 2019; 575(7784): 693-8.
[http://dx.doi.org/10.1038/s41586-019-1707-0] [PMID: 31634899]
[87]
Erdélyi K, Ditrói T, Johansson HJ, et al. Reprogrammed transsulfuration promotes basal-like breast tumor progression via realigning cellular cysteine persulfidation. Proc Natl Acad Sci 2021; 118(45): e2100050118.
[http://dx.doi.org/10.1073/pnas.2100050118] [PMID: 34737229]
[88]
Kraft VAN, Bezjian CT, Pfeiffer S, et al. GTP Cyclohydrolase 1/Tetrahydrobiopterin counteract ferroptosis through lipid remodeling. ACS Cent Sci 2020; 6(1): 41-53.
[http://dx.doi.org/10.1021/acscentsci.9b01063] [PMID: 31989025]
[89]
Yu H, Yang C, Jian L, et al. Sulfasalazine induced ferroptosis in breast cancer cells is reduced by the inhibitory effect of estrogen receptor on the transferrin receptor. Oncol Rep 2019; 42(2): 826-38.
[http://dx.doi.org/10.3892/or.2019.7189] [PMID: 31173262]
[90]
Bi J, Yang S, Li L, et al. Metadherin enhances vulnerability of cancer cells to ferroptosis. Cell Death Dis 2019; 10(10): 682.
[http://dx.doi.org/10.1038/s41419-019-1897-2] [PMID: 31527591]
[91]
Belkaid A, Duguay SR, Ouellette RJ, Surette ME. 17β-estradiol induces stearoyl-CoA desaturase-1 expression in estrogen receptor-positive breast cancer cells. BMC Cancer 2015; 15(1): 440.
[http://dx.doi.org/10.1186/s12885-015-1452-1] [PMID: 26022099]
[92]
Cook KL, Clarke PAG, Parmar J, et al. Knockdown of estrogen receptor‐α induces autophagy and inhibits antiestrogen‐mediated unfolded protein response activation, promoting ROS‐induced breast cancer cell death. FASEB J 2014; 28(9): 3891-905.
[http://dx.doi.org/10.1096/fj.13-247353] [PMID: 24858277]
[93]
Gao M, Monian P, Quadri N, Ramasamy R, Jiang X. Glutaminolysis and transferrin regulate ferroptosis. Mol Cell 2015; 59(2): 298-308.
[http://dx.doi.org/10.1016/j.molcel.2015.06.011] [PMID: 26166707]
[94]
Kwon MY, Park E, Lee SJ, Chung SW. Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death. Oncotarget 2015; 6(27): 24393-403.
[http://dx.doi.org/10.18632/oncotarget.5162] [PMID: 26405158]
[95]
Gammella E, Recalcati S, Rybinska I, Buratti P, Cairo G. Iron-induced damage in cardiomyopathy: Oxidative-dependent and independent mechanisms. Oxid Med Cell Longev 2015; 2015: 1-10.
[http://dx.doi.org/10.1155/2015/230182] [PMID: 25878762]
[96]
Zaffaroni N, Beretta GL. Nanoparticles for ferroptosis therapy in cancer. Pharmaceutics 2021; 13(11): 1785.
[http://dx.doi.org/10.3390/pharmaceutics13111785] [PMID: 34834199]
[97]
Hirschhorn T, Stockwell BR. The development of the concept of ferroptosis. Free Radic Biol Med 2019; 133: 130-43.
[http://dx.doi.org/10.1016/j.freeradbiomed.2018.09.043] [PMID: 30268886]
[98]
Yagoda N, von Rechenberg M, Zaganjor E, et al. RAS–RAF–MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 2007; 447(7146): 865-9.
[http://dx.doi.org/10.1038/nature05859] [PMID: 17568748]
[99]
Jaramillo MC, Zhang DD. The emerging role of the Nrf2–Keap1 signaling pathway in cancer. Genes Dev 2013; 27(20): 2179-91.
[http://dx.doi.org/10.1101/gad.225680.113] [PMID: 24142871]
[100]
Chio IIC, Jafarnejad SM, Ponz-Sarvise M, et al. NRF2 promotes tumor maintenance by modulating mRNA translation in pancreatic cancer. Cell 2016; 166(4): 963-76.
[http://dx.doi.org/10.1016/j.cell.2016.06.056] [PMID: 27477511]
[101]
Romero R, Sayin VI, Davidson SM, et al. Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis. Nat Med 2017; 23(11): 1362-8.
[http://dx.doi.org/10.1038/nm.4407] [PMID: 28967920]
[102]
Lien EC, Lyssiotis CA, Juvekar A, et al. Glutathione biosynthesis is a metabolic vulnerability in PI(3)K/Akt-driven breast cancer. Nat Cell Biol 2016; 18(5): 572-8.
[http://dx.doi.org/10.1038/ncb3341] [PMID: 27088857]
[103]
Wakabayashi N, Itoh K, Wakabayashi J, et al. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet 2003; 35(3): 238-45.
[http://dx.doi.org/10.1038/ng1248] [PMID: 14517554]
[104]
Kerins MJ, Ooi A. The roles of NRF2 in modulating cellular iron homeostasis. Antioxid Redox Signal 2018; 29(17): 1756-73.
[http://dx.doi.org/10.1089/ars.2017.7176] [PMID: 28793787]
[105]
Stockwell BR, Friedmann Angeli JP, Bayir H, et al. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell 2017; 171(2): 273-85.
[http://dx.doi.org/10.1016/j.cell.2017.09.021] [PMID: 28985560]
[106]
Jiang L, Kon N, Li T, et al. Ferroptosis as a p53-mediated activity during tumour suppression. Nature 2015; 520(7545): 57-62.
[http://dx.doi.org/10.1038/nature14344] [PMID: 25799988]
[107]
Jennis M, Kung CP, Basu S, et al. An African-specific polymorphism in the TP53 gene impairs p53 tumor suppressor function in a mouse model. Genes Dev 2016; 30(8): 918-30.
[http://dx.doi.org/10.1101/gad.275891.115] [PMID: 27034505]
[108]
Mai TT, Hamaï A, Hienzsch A, et al. Salinomycin kills cancer stem cells by sequestering iron in lysosomes. Nat Chem 2017; 9(10): 1025-33.
[http://dx.doi.org/10.1038/nchem.2778] [PMID: 28937680]
[109]
Lachaier E, Louandre C, Godin C, et al. Sorafenib induces ferroptosis in human cancer cell lines originating from different solid tumors. Anticancer Res 2014; 34(11): 6417-22.
[PMID: 25368241]
[110]
Yu M, Gai C, Li Z, et al. Targeted exosome‐encapsulated erastin induced ferroptosis in triple negative breast cancer cells. Cancer Sci 2019; 110(10): 3173-82.
[http://dx.doi.org/10.1111/cas.14181] [PMID: 31464035]
[111]
Xiong H, Wang C, Wang Z, Jiang Z, Zhou J, Yao J. Intracellular cascade activated nanosystem for improving ER+ breast cancer therapy through attacking GSH-mediated metabolic vulnerability. J Control Release 2019; 309: 145-57.
[http://dx.doi.org/10.1016/j.jconrel.2019.07.029] [PMID: 31348976]
[112]
Li Y, Wang X, Yan J, et al. Nanoparticle ferritin-bound erastin and rapamycin: A nanodrug combining autophagy and ferroptosis for anticancer therapy. Biomater Sci 2019; 7(9): 3779-87.
[http://dx.doi.org/10.1039/C9BM00653B] [PMID: 31211307]
[113]
Ma S, Dielschneider RF, Henson ES, et al. Ferroptosis and autophagy induced cell death occur independently after siramesine and lapatinib treatment in breast cancer cells. PLoS One 2017; 12(8): e0182921.
[http://dx.doi.org/10.1371/journal.pone.0182921] [PMID: 28827805]
[114]
Corna G, Santambrogio P, Minotti G, Cairo G. Doxorubicin paradoxically protects cardiomyocytes against iron-mediated toxicity: Role of reactive oxygen species and ferritin. J Biol Chem 2004; 279(14): 13738-45.
[http://dx.doi.org/10.1074/jbc.M310106200] [PMID: 14739295]
[115]
Sauzay C, Louandre C, Bodeau S, et al. Protein biosynthesis, a target of sorafenib, interferes with the unfolded protein response (UPR) and ferroptosis in hepatocellular carcinoma cells. Oncotarget 2018; 9(9): 8400-14.
[http://dx.doi.org/10.18632/oncotarget.23843] [PMID: 29492203]
[116]
An P, Gao Z, Sun K, et al. Photothermal-enhanced inactivation of glutathione peroxidase for ferroptosis sensitized by an autophagy promotor. ACS Appl Mater Interfaces 2019; 11(46): 42988-97.
[http://dx.doi.org/10.1021/acsami.9b16124] [PMID: 31650832]
[117]
An Y, Zhu J, Liu F, et al. Boosting the ferroptotic antitumor efficacy via site-specific amplification of tailored lipid peroxidation. ACS Appl Mater Interfaces 2019; 11(33): 29655-66.
[http://dx.doi.org/10.1021/acsami.9b10954] [PMID: 31359759]
[118]
Ma S, Henson ES, Chen Y, Gibson SB. Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis 2016; 7(7): e2307.
[http://dx.doi.org/10.1038/cddis.2016.208] [PMID: 27441659]
[119]
Lin HY, Ho HW, Chang YH, Wei CJ, Chu PY. The evolving role of ferroptosis in breast cancer: Translational implications present and future. Cancers 2021; 13(18): 4576.
[http://dx.doi.org/10.3390/cancers13184576] [PMID: 34572802]
[120]
Zhu J, Dai P, Liu F, et al. Upconverting nanocarriers enable triggered microtubule inhibition and concurrent ferroptosis induction for selective treatment of triple-negative breast cancer. Nano Lett 2020; 20(9): 6235-45.
[http://dx.doi.org/10.1021/acs.nanolett.0c00502] [PMID: 32804509]
[121]
Nieto C, Vega MA, Martín del Valle EM. Tailored-made polydopamine nanoparticles to induce ferroptosis in breast cancer cells in combination with chemotherapy. Int J Mol Sci 2021; 22(6): 3161.
[http://dx.doi.org/10.3390/ijms22063161] [PMID: 33808898]
[122]
Kato I, Kasukabe T, Kumakura S. Menin MLL inhibitors induce ferroptosis and enhance the anti proliferative activity of auranofin in several types of cancer cells. Int J Oncol 2020; 57(4): 1057-71.
[http://dx.doi.org/10.3892/ijo.2020.5116] [PMID: 32945449]
[123]
Du J, Wang L, Huang X, et al. Shuganning injection, a traditional Chinese patent medicine, induces ferroptosis and suppresses tumor growth in triple-negative breast cancer cells. Phytomedicine 2021; 85: 153551.
[124]
von Hagens C, Walter-Sack I, Goeckenjan M, et al. Prospective open uncontrolled phase I study to define a well-tolerated dose of oral artesunate as add-on therapy in patients with metastatic breast cancer (ARTIC M33/2). Breast Cancer Res Treat 2017; 164(2): 359-69.
[http://dx.doi.org/10.1007/s10549-017-4261-1] [PMID: 28439738]
[125]
Zhang H, Ge Z, Wang Z, Gao Y, Wang Y, Qu X. Circular RNA RHOT1 promotes progression and inhibits ferroptosis via mir-106a-5p/STAT3 axis in breast cancer. Aging 2021; 13(6): 8115-26.
[http://dx.doi.org/10.18632/aging.202608] [PMID: 33686957]
[126]
Sun D, Li YC, Zhang XY. Lidocaine promoted ferroptosis by targeting miR-382-5p/SLC7A11 axis in ovarian and breast cancer. Front Pharmacol 2021; 12: 681223.
[http://dx.doi.org/10.3389/fphar.2021.681223] [PMID: 34122108]
[127]
Lee N, Carlisle AE, Peppers A, et al. xCT-driven expression of GPX4 determines sensitivity of breast cancer cells to ferroptosis inducers. Antioxidants 2021; 10(2): 317.
[http://dx.doi.org/10.3390/antiox10020317] [PMID: 33672555]
[128]
Wen Y, Chen H, Zhang L, et al. Glycyrrhetinic acid induces oxidative/nitrative stress and drives ferroptosis through activating NADPH oxidases and iNOS, and depriving glutathione in triple-negative breast cancer cells. Free Radic Biol Med 2021; 173: 41-51.
[http://dx.doi.org/10.1016/j.freeradbiomed.2021.07.019] [PMID: 34271106]
[129]
Zhou Y, Yang J, Chen C, et al. Polyphyllin III-induced ferroptosis in MDA-MB-231 triple-negative breast cancer cells can be protected against by KLF4-mediated upregulation of xCT. Front Pharmacol 2021; 12: 670224.
[http://dx.doi.org/10.3389/fphar.2021.670224] [PMID: 34040532]
[130]
Beatty A, Singh T, Tyurina YY, et al. Ferroptotic cell death triggered by conjugated linolenic acids is mediated by ACSL1. Nat Commun 2021; 12(1): 2244.
[http://dx.doi.org/10.1038/s41467-021-22471-y] [PMID: 33854057]
[131]
Bjarnadottir O, Romero Q, Bendahl PO, et al. Targeting HMG-CoA reductase with statins in a window-of-opportunity breast cancer trial. Breast Cancer Res Treat 2013; 138(2): 499-508.
[http://dx.doi.org/10.1007/s10549-013-2473-6] [PMID: 23471651]
[132]
Garwood ER, Kumar AS, Baehner FL, et al. Fluvastatin reduces proliferation and increases apoptosis in women with high grade breast cancer. Breast Cancer Res Treat 2010; 119(1): 137-44.
[http://dx.doi.org/10.1007/s10549-009-0507-x] [PMID: 19728082]
[133]
Hubackova S, Davidova E, Boukalova S, et al. Replication and ribosomal stress induced by targeting pyrimidine synthesis and cellular checkpoints suppress p53-deficient tumors. Cell Death Dis 2020; 11(2): 110.
[http://dx.doi.org/10.1038/s41419-020-2224-7] [PMID: 32034120]
[134]
Mohamad Fairus AK, Choudhary B, Hosahalli S, Kavitha N, Shatrah O. Dihydroorotate dehydrogenase (DHODH) inhibitors affect ATP depletion, endogenous ROS and mediate S-phase arrest in breast cancer cells. Biochimie 2017; 135: 154-63.
[http://dx.doi.org/10.1016/j.biochi.2017.02.003] [PMID: 28196676]
[135]
Jiang Z, Lim SO, Yan M, et al. TYRO3 induces anti–PD-1/PD-L1 therapy resistance by limiting innate immunity and tumoral ferroptosis. J Clin Invest 2021; 131(8): e139434.
[http://dx.doi.org/10.1172/JCI139434] [PMID: 33855973]
[136]
Ding Y, Chen X, Liu C, et al. Identification of a small molecule as inducer of ferroptosis and apoptosis through ubiquitination of GPX4 in triple negative breast cancer cells. J Hematol Oncol 2021; 14(1): 19.
[http://dx.doi.org/10.1186/s13045-020-01016-8] [PMID: 33472669]
[137]
Song R, Li T, Ye J, et al. Acidity‐activatable dynamic nanoparticles boosting ferroptotic cell death for immunotherapy of cancer. Adv Mater 2021; 33(31): 2101155.
[http://dx.doi.org/10.1002/adma.202101155] [PMID: 34170581]
[138]
Wu X, Liu C, Li Z, et al. Regulation of GSK3β/Nrf2 signaling pathway modulated erastin-induced ferroptosis in breast cancer. Mol Cell Biochem 2020; 473(1-2): 217-28.
[http://dx.doi.org/10.1007/s11010-020-03821-8] [PMID: 32642794]

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