Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities
Caiguo Zhang, Fan Zhang
Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities
Excess iron is tightly associated with tumorigenesis in multiple human cancer types through a variety of mechanisms including catalyzing the formation of mutagenic hydroxyl radicals, regulating DNA replication, repair and cell cycle progression, affecting signal transduction in cancer cells, and acting as an essential nutrient for proliferating tumor cells. Thus, multiple therapeutic strategies based on iron deprivation have been developed in cancer therapy. During the past few years, our understanding of genetic association and molecular mechanisms between iron and tumorigenesis has expanded enormously. In this review, we briefly summarize iron homeostasis in mammals, and discuss recent progresses in understanding the aberrant iron metabolism in numerous cancer types, with a focus on studies revealing altered signal transduction in cancer cells.
Iron tumorigenesis / p53 / Wnt / DNA repair / cell cycle
[1] |
Chaston TB, Richardson DR (2003) Iron chelators for the treatment of iron overload disease: relationship between structure, redox activity, and toxicity. Am J Hematol73: 200-210
CrossRef
Google scholar
|
[2] |
Chen G, Fillebeen C, Wang J, Pantopoulos K (2007) Overexpression of iron regulatory protein 1 suppresses growth of tumor xenografts. Carcinogenesis28: 785-791
CrossRef
Google scholar
|
[3] |
Chen Y, Zhang Z, Yang K, Du J, Xu Y, Liu S (2014) Myeloid zincfinger 1 (MZF-1) suppresses prostate tumor growth through enforcing ferroportin-conducted iron egress. Oncogene
CrossRef
Google scholar
|
[4] |
Cheng Z, Dai LL, Song YN, Kang Y, Si JM, Xia J, Liu YF (2014) Regulatory effect of iron regulatory protein-2 on iron metabolism in lung cancer. Genet Mol Res13: 5514-5522
CrossRef
Google scholar
|
[5] |
Cho H, Kim JH (2009) Lipocalin2 expressions correlate significantly with tumor differentiation in epithelial ovarian cancer. J Histochem Cytochem57: 513-521
CrossRef
Google scholar
|
[6] |
Choi AM, Alam J (1996) Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidantinduced lung injury. Am J Respir Cell Mol Biol15: 9-19
CrossRef
Google scholar
|
[7] |
Crepin R, Goenaga AL, Jullienne B, Bougherara H, Legay C, Benihoud K, Marks JD, Poul MA (2010) Development of human single-chain antibodies to the transferrin receptor that effectively antagonize the growth of leukemias and lymphomas. Cancer Res70: 5497-5506
CrossRef
Google scholar
|
[8] |
Daniels TR, Bernabeu E, Rodriguez JA, Patel S, Kozman M, Chiappetta DA, Holler E, Ljubimova JY, Helguera G, Penichet ML (2012) The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta1820: 291-317
CrossRef
Google scholar
|
[9] |
Dayani PN, Bishop MC, Black K, Zeltzer PM (2004) Desferoxamine (DFO)-mediated iron chelation: rationale for a novel approach to therapy for brain cancer. J Neurooncol67: 367-377
CrossRef
Google scholar
|
[10] |
Denic S, Agarwal MM (2007) Nutritional iron deficiency: an evolutionary perspective. Nutrition23: 603-614
CrossRef
Google scholar
|
[11] |
Dongiovanni P, Fracanzani AL, Cairo G, Megazzini CP, Gatti S, Rametta R, Fargion S, Valenti L (2010) Iron-dependent regulation of MDM2 influences p53 activity and hepatic carcinogenesis. Am J Pathol176: 1006-1017
CrossRef
Google scholar
|
[12] |
Duarte DC, Nicolau A, Teixeira JA, Rodrigues LR (2011) The effect of bovine milk lactoferrin on human breast cancer cell lines. J Dairy Sci94: 66-76
CrossRef
Google scholar
|
[13] |
Dunn LL, Suryo Rahmanto Y, Richardson DR (2007) Iron uptake and metabolism in the new millennium. Trends Cell Biol17: 93-100
CrossRef
Google scholar
|
[14] |
Eberhard Y, McDermott SP, Wang X, Gronda M, Venugopal A, Wood TE, Hurren R, Datti A, Batey RA, Wrana J
CrossRef
Google scholar
|
[15] |
Emanuele D, Tuason I, Edwards QT (2014) HFE-associated hereditary hemochromatosis: overview of genetics and clinical implications for nurse practitioners in primary care settings. J Am Assoc Nurse Pract26: 113-122
|
[16] |
Enyedy EA, Primik MF, Kowol CR, Arion VB, Kiss T, Keppler BK (2011) Interaction of Triapine and related thiosemicarbazones with iron(III)/(II) and gallium(III): a comparative solution equilibrium study. Dalton Trans40: 5895-5905
CrossRef
Google scholar
|
[17] |
Fernandez CA, Yan L, Louis G, Yang J, Kutok JL, Moses MA (2005) The matrix metalloproteinase-9/neutrophil gelatinase-associated lipocalin complex plays a role in breast tumor growth and is present in the urine of breast cancer patients. Clin Cancer Res11: 5390-5395
CrossRef
Google scholar
|
[18] |
Forsythe JA, Jiang BH, Iyer NV, Agani F, Leung SW, Koos RD, Semenza GL (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol16: 4604-4613
|
[19] |
Fu D, Richardson DR (2007) Iron chelation and regulation of the cell cycle: 2 mechanisms of posttranscriptional regulation of the universal cyclin-dependent kinase inhibitor p21CIP1/WAF1 by iron depletion. Blood110: 752-761
CrossRef
Google scholar
|
[20] |
Gkouvatsos K, Papanikolaou G, Pantopoulos K (2012) Regulation of iron transport and the role of transferrin. Biochim Biophys Acta1820: 188-202
CrossRef
Google scholar
|
[21] |
Hamalainen P, Saltevo J, Kautiainen H, Mantyselka P, Vanhala M (2012) Erythropoietin, ferritin, haptoglobin, hemoglobin and transferrin receptor in metabolic syndrome: a case control study. Cardiovasc Diabetol11: 116
CrossRef
Google scholar
|
[22] |
Hewitson KS, McNeill LA, Elkins JM, Schofield CJ (2003) The role of iron and 2-oxoglutarate oxygenases in signalling. Biochem Soc Trans31: 510-515
CrossRef
Google scholar
|
[23] |
Hohaus S, Massini G, Giachelia M, Vannata B, Bozzoli V, Cuccaro A, D’Alo F, Larocca LM, Raymakers RA, Swinkels DW
CrossRef
Google scholar
|
[24] |
Hong CC, Ambrosone CB, Ahn J, Choi JY, McCullough ML, Stevens VL, Rodriguez C, Thun MJ, Calle EE (2007) Genetic variability in iron-related oxidative stress pathways (Nrf2, NQ01, NOS3, and HO-1), iron intake, and risk of postmenopausal breast cancer. Cancer Epidemiol Biomark Prev16: 1784-1794
CrossRef
Google scholar
|
[25] |
Hou Y, Zhang S, Wang L, Li J, Qu G, He J, Rong H, Ji H, Liu S (2012) Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element. Gene511: 398-403
CrossRef
Google scholar
|
[26] |
Iwasaki K, Ray PD, Huang BW, Sakamoto K, Kobayashi T, Tsuji Y (2013) Role of AMP-activated protein kinase in ferritin H gene expression by resveratrol in human T cells. Biochemistry52: 5075-5083
CrossRef
Google scholar
|
[27] |
Jakszyn PG, Allen NE, Lujan-Barroso L, Gonzalez CA, Key TJ, Fonseca-Nunes A, Tjonneland A, Fons-Johnsen N, Overvad K, Teucher B
CrossRef
Google scholar
|
[28] |
Jiang XP, Elliott RL, Head JF (2010) Manipulation of iron transporter genes results in the suppression of human and mouse mammary adenocarcinomas. Anticancer Res30: 759-765
|
[29] |
Josson S, Matsuoka Y, Gururajan M, Nomura T, Huang WC, Yang X, Lin JT, Bridgman R, Chu CY, Johnstone PA
CrossRef
Google scholar
|
[30] |
Kalousova M, Krechler T, Jachymova M, Kubena AA, Zak A, Zima T (2012) Ferritin as an independent mortality predictor in patients with pancreas cancer. Results of a pilot study. Tumour Biol33: 1695-1700
CrossRef
Google scholar
|
[31] |
Kaplan CD, Kaplan J (2009) Iron acquisition and transcriptional regulation. Chem Rev109: 4536-4552
CrossRef
Google scholar
|
[32] |
Keith B, Johnson RS, Simon MC (2012) HIF1alpha and HIF2alpha: sibling rivalry in hypoxic tumour growth and progression. Nat Rev Cancer12: 9-22
|
[33] |
Koc M, Taysi S, Sezen O, Bakan N (2003) Levels of some acutephase proteins in the serum of patients with cancer during radiotherapy. Biol Pharm Bull26: 1494-1497
CrossRef
Google scholar
|
[34] |
Koreth J, Antin JH (2010) Iron overload in hematologic malignancies and outcome of allogeneic hematopoietic stem cell transplantation. Haematologica95: 364-366
CrossRef
Google scholar
|
[35] |
Kowdley KV (2004) Iron, hemochromatosis, and hepatocellular carcinoma. Gastroenterology127: S79-86
CrossRef
Google scholar
|
[36] |
Kukulj S, Jaganjac M, Boranic M, Krizanac S, Santic Z, Poljak-Blazi M (2010) Altered iron metabolism, inflammation, transferrin receptors, and ferritin expression in non-small-cell lung cancer. Med Oncol27: 268-277
CrossRef
Google scholar
|
[37] |
Kumar D, Viberg J, Nilsson AK, Chabes A (2010) Highly mutagenic and severely imbalanced dNTP pools can escape detection by the S-phase checkpoint. Nucleic Acids Res38: 3975-3983
CrossRef
Google scholar
|
[38] |
Lee PJ, Jiang BH, Chin BY, Iyer NV, Alam J, Semenza GL, Choi AM (1997) Hypoxia-inducible factor-1 mediates transcriptional activation of the heme oxygenase-1 gene in response to hypoxia. J Biol Chem272: 5375-5381
CrossRef
Google scholar
|
[39] |
Lee SH, Pyo CW, Hahm DH, Kim J, Choi SY (2009) Iron-saturated lactoferrin stimulates cell cycle progression through PI3K/Akt pathway. Mol Cells28: 37-42
CrossRef
Google scholar
|
[40] |
Leng X, Ding T, Lin H, Wang Y, Hu L, Hu J, Feig B, Zhang W, Pusztai L, Symmans WF
CrossRef
Google scholar
|
[41] |
Leng X, Wu Y, Arlinghaus RB (2011) Relationships of lipocalin 2 with breast tumorigenesis and metastasis. J Cell Physiol226: 309-314
CrossRef
Google scholar
|
[42] |
Leung L, Radulovich N, Zhu CQ, Organ S, Bandarchi B, Pintilie M, To C, Panchal D, Tsao MS (2012) Lipocalin2 promotes invasion, tumorigenicity and gemcitabine resistance in pancreatic ductal adenocarcinoma. PLoS One7: e46677
CrossRef
Google scholar
|
[43] |
Lill R, Hoffmann B, Molik S, Pierik AJ, Rietzschel N, Stehling O, Uzarska MA, Webert H, Wilbrecht C, Muhlenhoff U (2012) The role of mitochondria in cellular iron-sulfur protein biogenesis and iron metabolism. Biochim Biophys Acta1823: 1491-1508
CrossRef
Google scholar
|
[44] |
Lin X, Yang H, Zhou L, Guo Z (2011) Nrf2-dependent induction of NQO1 in mouse aortic endothelial cells overexpressing catalase. Free Radic Biol Med51: 97-106
CrossRef
Google scholar
|
[45] |
Lok CN, Ponka P (1999) Identification of a hypoxia response element in the transferrin receptor gene. J Biol Chem274: 24147-24152
CrossRef
Google scholar
|
[46] |
Lovejoy DB, Richardson DR (2003) Iron chelators as anti-neoplastic agents: current developments and promise of the PIH class of chelators. Curr Med Chem10: 1035-1049
CrossRef
Google scholar
|
[47] |
MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell17: 9-26
CrossRef
Google scholar
|
[48] |
MacKenzie EL, Iwasaki K, Tsuji Y (2008) Intracellular iron transport and storage: from molecular mechanisms to health implications. Antioxid Redox Signal10: 997-1030
CrossRef
Google scholar
|
[49] |
Maes K, Nemeth E, Roodman GD, Huston A, Esteve F, Freytes C, Callander N, Katodritou E, Tussing-Humphreys L, Rivera S
CrossRef
Google scholar
|
[50] |
Mannelqvist M, Stefansson IM, Wik E, Kusonmano K, Raeder MB, Oyan AM, Kalland KH, Moses MA, Salvesen HB, Akslen LA (2012) Lipocalin 2 expression is associated with aggressive features of endometrial cancer. BMC Cancer12: 169
CrossRef
Google scholar
|
[51] |
Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature454: 436-444
CrossRef
Google scholar
|
[52] |
Martin JH, Alalami O, Yaqoob F (2000) Differential effects of retinoids on nitric oxide production by promonocytic U937 cells and ZR-75-1 human breast cancer cells. Oncol Rep7: 219-223
|
[53] |
Miller JL (2013) Iron deficiency anemia: a common and curable disease. Cold Spring Harb Perspect Med3: a011866
CrossRef
Google scholar
|
[54] |
Miyabe I, Kunkel TA, Carr AM (2011) The major roles of DNA polymerases epsilon and delta at the eukaryotic replication fork are evolutionarily conserved. PLoS Genet7: e1002407
CrossRef
Google scholar
|
[55] |
Molina-Montes E, Wark PA, Sanchez MJ, Norat T, Jakszyn P, LujanBarroso L, Michaud DS, Crowe F, Allen N, Khaw KT
CrossRef
Google scholar
|
[56] |
Moser JC, Rawal M, Wagner BA, Du J, Cullen JJ, Buettner GR (2013) Pharmacological ascorbate and ionizing radiation (IR) increase labile iron in pancreatic cancer. Redox Biol2: 22-27
CrossRef
Google scholar
|
[57] |
Muckenthaler MU, Galy B, Hentze MW (2008) Systemic iron homeostasis and the iron-responsive element/iron-regulatory protein (IRE/IRP) regulatory network. Annu Rev Nutr28: 197-213
CrossRef
Google scholar
|
[58] |
Mukhopadhyay CK, Mazumder B, Fox PL (2000) Role of hypoxiainducible factor-1 in transcriptional activation of ceruloplasmin by iron deficiency. J Biol Chem275: 21048-21054
CrossRef
Google scholar
|
[59] |
Munoz M, Gomez-Ramirez S, Martin-Montanez E, Auerbach M (2014) Perioperative anemia management in colorectal cancer patients: a pragmatic approach. World J Gastroenterol20: 1972-1985
CrossRef
Google scholar
|
[60] |
Oh WK (2002) The evolving role of estrogen therapy in prostate cancer. Clin Prostate Cancer1: 81 -89
CrossRef
Google scholar
|
[61] |
Ornstein DL, Zacharski LR (2007) Iron stimulates urokinase plasminogen activator expression and activates NF-kappa B in human prostate cancer cells. Nutr Cancer58: 115-126
CrossRef
Google scholar
|
[62] |
Orrenius S, Nicotera P, Zhivotovsky B (2011) Cell death mechanisms and their implications in toxicology. Toxicol Sci119: 3-19
CrossRef
Google scholar
|
[63] |
Osborne NJ, Gurrin LC, Allen KJ, Constantine CC, Delatycki MB, McLaren CE, Gertig DM, Anderson GJ, Southey MC, Olynyk JK
CrossRef
Google scholar
|
[64] |
Pantopoulos K, Porwal SK, Tartakoff A, Devireddy L (2012) Mechanisms of mammalian iron homeostasis. Biochemistry 51: 5705-5724
CrossRef
Google scholar
|
[65] |
Park KS, Kim H, Kim NG, Cho SY, Choi KH, Seong JK, Paik YK (2002) Proteomic analysis and molecular characterization of tissue ferritin light chain in hepatocellular carcinoma. Hepatology35: 1459-1466
CrossRef
Google scholar
|
[66] |
Peyssonnaux C, Zinkernagel AS, Schuepbach RA, Rankin E, Vaulont S, Haase VH, Nizet V, Johnson RS (2007) Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J Clin Invest117: 1926-1932
CrossRef
Google scholar
|
[67] |
Preston BD, Albertson TM, Herr AJ (2010) DNA replication fidelity and cancer. Semin Cancer Biol20: 281 -293
CrossRef
Google scholar
|
[68] |
Pusatcioglu CK, Nemeth E, Fantuzzi G, Llor X, Freels S, TussingHumphreys L, Cabay RJ, Linzmeier R, Ng D, Clark J
CrossRef
Google scholar
|
[69] |
Radulescu S, Brookes MJ, Salgueiro P, Ridgway RA, McGhee E, Anderson K, Ford SJ, Stones DH, Iqbal TH, Tselepis C
CrossRef
Google scholar
|
[70] |
Richardson DR, Kalinowski DS, Richardson V, Sharpe PC, Lovejoy DB, Islam M, Bernhardt PV (2009) 2-Acetylpyridine thiosemicarbazones are potent iron chelators and antiproliferative agents: redox activity, iron complexation and characterization of their antitumor activity. J Med Chem52: 1459-1470
CrossRef
Google scholar
|
[71] |
Romero A, Ramos E, de Los Rios C, Egea J, Del Pino J, Reiter RJ (2014) A review of metal-catalyzed molecular damage: protection by melatonin. J Pineal Res56: 343-370
CrossRef
Google scholar
|
[72] |
Rossi E (2005) Hepcidin – the iron regulatory hormone. Clin Biochem Rev26: 47-49
|
[73] |
Rouault TA (2003) How mammals acquire and distribute iron needed for oxygen-based metabolism. PLoS Biol1: E79
CrossRef
Google scholar
|
[74] |
Rouault TA (2006) The role of iron regulatory proteins in mammalian iron homeostasis and disease. Nat Chem Biol2: 406-414
CrossRef
Google scholar
|
[75] |
Sakurai K, Sohda T, Ueda S, Tanaka T, Hirano G, Yokoyama K, Mori hara D, Aanan A, Takeyama Y, Irie M
|
[76] |
Sarkar A, Sil PC (2014) Iron oxide nanoparticles mediated cytotoxicity via PI3K/AKT pathway: role of quercetin. Food Chem Toxicol71: 106-115
CrossRef
Google scholar
|
[77] |
Shen J, Sheng X, Chang Z, Wu Q, Wang S, Xuan Z, Li D, Wu Y, Shang Y, Kong X
CrossRef
Google scholar
|
[78] |
Shiiba M, Saito K, Fushimi K, Ishigami T, Shinozuka K, Nakashima D, Kouzu Y, Koike H, Kasamatsu A, Sakamoto Y
|
[79] |
Shpyleva SI, Tryndyak VP, Kovalchuk O, Starlard-Davenport A, Chekhun VF, Beland FA, Pogribny IP (2011) Role of ferritin alterations in human breast cancer cells. Breast Cancer Res Treat126: 63-71
CrossRef
Google scholar
|
[80] |
Sica A, Allavena P, Mantovani A (2008) Cancer related inflammation: the macrophage connection. Cancer Lett267: 204-215
CrossRef
Google scholar
|
[81] |
Siriwardana G, Seligman PA (2013) Two cell cycle blocks caused by iron chelation of neuroblastoma cells: separating cell cycle events associated with each block. Physiol Rep1: e00176
CrossRef
Google scholar
|
[82] |
Song S, Christova T, Perusini S, Alizadeh S, Bao RY, Miller BW, Hurren R, Jitkova Y, Gronda M, Isaac M
CrossRef
Google scholar
|
[83] |
Stocker R (1990) Induction of haem oxygenase as a defence against oxidative stress. Free Radic Res Commun9: 101 -112
CrossRef
Google scholar
|
[84] |
Tacchini L, Bianchi L, Bernelli-Zazzera A, Cairo G (1999) Transferrin receptor induction by hypoxia. HIF-1-mediated transcriptional activation and cell-specific post-transcriptional regulation. J Biol Chem274: 24142-24146
CrossRef
Google scholar
|
[85] |
Tammariello AE, Milner JA (2010) Mouse models for unraveling the importance of diet in colon cancer prevention. J Nutr Biochem21: 77-88
CrossRef
Google scholar
|
[86] |
Tan MG, Kumarasinghe MP, Wang SM, Ooi LL, Aw SE, Hui KM (2009) Modulation of iron-regulatory genes in human hepatocellular carcinoma and its physiological consequences. Exp Biol Med (Maywood)234: 693-702
CrossRef
Google scholar
|
[87] |
Tenga MJ, Lazar IM (2014) Proteomic study reveals a functional network of cancer markers in the G1-Stage of the breast cancer cell cycle. BMC Cancer14: 710
CrossRef
Google scholar
|
[88] |
Thomas C, Mackey MM, Diaz AA, Cox DP (2009) Hydroxyl radical is produced via the Fenton reaction in submitochondrial particles under oxidative stress: implications for diseases associated with iron accumulation. Redox Rep14: 102-108
CrossRef
Google scholar
|
[89] |
Torti SV, Torti FM (2013) Iron and cancer: more ore to be mined. Nat Rev Cancer13: 342-355
CrossRef
Google scholar
|
[90] |
Trachootham D, Lu W, Ogasawara MA, Nilsa RD, Huang P (2008) Redox regulation of cell survival. Antioxid Redox Signal10: 1343-1374
CrossRef
Google scholar
|
[91] |
Tsui KH, Chung LC, Wang SW, Feng TH, Chang PL, Juang HH (2013) Hypoxia upregulates the gene expression of mitochondrial aconitase in prostate carcinoma cells. J Mol Endocrinol51: 131 -141
CrossRef
Google scholar
|
[92] |
Vakkala M, Paakko P, Soini Y (2000) eNOS expression is associated with the estrogen and progesterone receptor status in invasive breast carcinoma. Int J Oncol17: 667-671
|
[93] |
Valerio LG (2007) Mammalian iron metabolism. Toxicol Mech. Methods17: 497-517
CrossRef
Google scholar
|
[94] |
Vescio RA, Connors KM, Bordin GM, Robb JA, Youngkin T, Umbreit JN, Hoffman RM (1990) The distinction of small cell and nonsmall cell lung cancer by growth in native-state histoculture. Cancer Res50: 6095-6099
|
[95] |
von Maltzahn J, Chang NC, Bentzinger CF, Rudnicki MA (2012) Wnt signaling in myogenesis. Trends Cell Biol22: 602-609
CrossRef
Google scholar
|
[96] |
Wang J, Pantopoulos K (2002) Conditional derepression of ferritin synthesis in cells expressing a constitutive IRP1 mutant. Mol Cell Biol22: 4638-4651
CrossRef
Google scholar
|
[97] |
Wang J, Li Q, Ou Y, Han Z, Li K, Wang P, Zhou S (2011) Inhibition of tumor growth by recombinant adenovirus containing human lactoferrin through inducing tumor cell apoptosis in mice bearing EMT6 breast cancer. Arch Pharm Res34: 987-995
CrossRef
Google scholar
|
[98] |
Wang N, Wei H, Yin D, Lu Y, Zhang Y, Jiang D, Jiang Y, Zhang S (2014) Cyclin D1b overexpression inhibits cell proliferation and induces cell apoptosis in cervical cancer cells in vitro and in vivo. Int J Clin Exp Pathol7: 4016-4023
|
[99] |
Ward PP, Mendoza-Meneses M, Cunningham GA, Conneely OM (2003) Iron status in mice carrying a targeted disruption of lactoferrin. Mol Cell Biol23: 178-185
CrossRef
Google scholar
|
[100] |
Wu Y, Brosh RM Jr (2012) DNA helicase and helicase-nuclease enzymes with a conserved iron-sulfur cluster. Nucleic Acids Res40: 4247-4260
CrossRef
Google scholar
|
[101] |
Wyllie S, Liehr JG (1997) Release of iron from ferritin storage by redox cycling of stilbene and steroid estrogen metabolites: a mechanism of induction of free radical damage by estrogen. Arch Biochem Biophys346: 180-186
CrossRef
Google scholar
|
[102] |
Xiong W, Wang L, Yu F (2014) Regulation of cellular iron metabolism and its implications in lung cancer progression. Med Oncol31: 28
CrossRef
Google scholar
|
[103] |
Xue X, Shah YM (2013) Intestinal iron homeostasis and colon tumorigenesis. Nutrients5: 2333-2351
CrossRef
Google scholar
|
[104] |
Xue X, Taylor M, Anderson E, Hao C, Qu A, Greenson JK, Zimmermann EM, Gonzalez FJ, Shah YM (2012) Hypoxiainducible factor-2alpha activation promotes colorectal cancer progression by dysregulating iron homeostasis. Cancer Res72: 2285-2293
CrossRef
Google scholar
|
[105] |
Yang J, Bielenberg DR, Rodig SJ, Doiron R, Clifton MC, Kung AL, Strong RK, Zurakowski D, Moses MA (2009) Lipocalin 2 promotes breast cancer progression. Proc Natl Acad Sci U S A106: 3913-3918
CrossRef
Google scholar
|
[106] |
Yang J, McNeish B, Butterfield C, Moses MA (2013) Lipocalin 2 is a novel regulator of angiogenesis in human breast cancer. FASEB J27: 45-50
CrossRef
Google scholar
|
[107] |
Yildirim A, Meral M, Kaynar H, Polat H, Ucar EY (2007) Relationship between serum levels of some acute-phase proteins and stage of disease and performance status in patients with lung cancer. Med Sci Monit13: CR195-200
|
[108] |
Yu Y, Wong J, Lovejoy DB, Kalinowski DS, Richardson DR (2006) Chelators at the cancer coalface: desferrioxamine to Triapine and beyond. Clin Cancer Res12: 6876-6883
CrossRef
Google scholar
|
[109] |
Zhang C (2014) Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control. Protein Cell5: 750-760
CrossRef
Google scholar
|
[110] |
Zhang F, Wang W, Tsuji Y, Torti SV, Torti FM (2008) Posttranscriptional modulation of iron homeostasis during p53-dependent growth arrest. J Biol Chem283: 33911-33918
CrossRef
Google scholar
|
[111] |
Zhang F, Tao Y, Zhang Z, Guo X, An P, Shen Y, Wu Q, Yu Y, Wang F (2012) Metalloreductase Steap3 coordinates the regulation of iron homeostasis and inflammatory responses. Haematologica97: 1826-1835
CrossRef
Google scholar
|
[112] |
Zhang C, Liu G, Huang M (2014) Ribonucleotide reductase metallocofactor: assembly, maintenance and inhibition. Front Biol (Beijing)9: 104-113
CrossRef
Google scholar
|
[113] |
Zhao N, Gao J, Enns CA, Knutson MD (2010) ZRT/IRT-like protein 14 (ZIP14) promotes the cellular assimilation of iron from transferrin. J Biol Chem285: 32141-32150
CrossRef
Google scholar
|
/
〈 | 〉 |