Expanding horizons in iron chelation and the treatment of cancer: Role of iron in the regulation of ER stress and the epithelial-mesenchymal transition

Biochimica et Biophysica Acta - Reviews on Cancer

Volumn 1845, Issue 2, 2014, Pages 166-181

  Lane, Darius J R ^a   Mills, Thomas M ^a   Shafie, Nurul H ^a   Merlot, Angelica M ^a   Saleh Moussa, Rayan ^a   Kalinowski, Danuta S ^a   Kovacevic, Zaklina ^a   Richardson, Des R ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

EMT; Epithelial mesenchymal transition; ER stress; Iron chelation; PERK; Thiosemicarbazone

Indexed keywords

3 AMINOPICOLINALDEHYDE THIOSEMICARBAZONE; ACTIVATING TRANSCRIPTION FACTOR 6; ANTINEOPLASTIC AGENT; BETA CATENIN; CYCLIN DEPENDENT KINASE 2; DEFEROXAMINE; DI 2 PYRIDYLKETONE 4 CYCLOHEXYL 4 METHYL 3 THIOSEMICARBAZONE; DI 2 PYRIDYLKETONE 4,4 DIMETHYL 3 THIOSEMICARBAZONE; DNA; GLUCOSE REGULATED PROTEIN 78; GLYCOGEN SYNTHASE KINASE 3BETA; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 153; HYPOXIA INDUCIBLE FACTOR 1; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; IRON; IRON CHELATING AGENT; MYC PROTEIN; OXYHEMOGLOBIN; PROTEIN IRE1; PROTEIN KINASE; PROTEIN KINASE LIKE ER KINASE; PROTEIN P53; REACTIVE OXYGEN METABOLITE; RIBONUCLEOTIDE REDUCTASE; THIOSEMICARBAZONE; TRANSCRIPTION FACTOR SNAIL; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UNINDEXED DRUG; UVOMORULIN; X BOX BINDING PROTEIN 1;

ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; AUTOPHAGY; CANCER INHIBITION; CANCER RADIOTHERAPY; CANCER SURVIVAL; CANCER THERAPY; CARDIOTOXICITY; CELL CYCLE ARREST; CELL CYCLE PROGRESSION; CELL DIFFERENTIATION; CELL FUNCTION; CELL JUNCTION; CELL PROLIFERATION; DNA REPAIR; DNA SYNTHESIS; DRUG HALF LIFE; DRUG MEGADOSE; DRUG METABOLISM; DRUG PENETRATION; DRUG POTENCY; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG TARGETING; ENDOPLASMIC RETICULUM STRESS; ENZYME INHIBITION; EPITHELIAL MESENCHYMAL TRANSITION; FATIGUE; GENE; GENE EXPRESSION; HEART MUSCLE FIBROSIS; HUMAN; HYDROPHILICITY; HYPOTENSION; HYPOXIA; IRON CHELATION; IRON DEPLETION; IRON KINETICS; IRON METABOLISM; IRON TRANSPORT; KIDNEY METASTASIS; LOW DRUG DOSE; LYSOSOME; METASTASIS; METHEMOGLOBINEMIA; NAUSEA; NDRG1 GENE; NEOPLASM; NEUTROPENIA; NONHUMAN; OXIDATION REDUCTION REACTION; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FOLDING; PROTEIN PHOSPHORYLATION; PROTEIN UNFOLDING; REVIEW; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS; UNFOLDED PROTEIN RESPONSE;

EMT; EPITHELIAL-MESENCHYMAL TRANSITION; ER STRESS; IRON CHELATION; PERK; THIOSEMICARBAZONE;

DNA, NEOPLASM; ENDOPLASMIC RETICULUM STRESS; EPITHELIAL-MESENCHYMAL TRANSITION; HUMANS; IRON; IRON CHELATING AGENTS; NEOPLASM METASTASIS; NEOPLASMS; REACTIVE OXYGEN SPECIES; RIBONUCLEOTIDE REDUCTASES;

EID: 84896695093     PISSN: 0304419X     EISSN: 18792561     Source Type: Journal    
DOI: 10.1016/j.bbcan.2014.01.005     Document Type: Review

References (193)

1. Ferlay J., Shin H.R., Bray F., Forman D., Mathers C., Parkin D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer 2010, 127:2893-2917.
2. Bray F., Jemal A., Grey N., Ferlay J., Forman D. Global cancer transitions according to the Human Development Index (2008-2030): a population-based study. Lancet Oncol. 2012, 13:790-801.
3. Rang H.P., Dale M.M., Ritter J.M., Flower R. Pharmacology 2011, Churchill Livingstone, London. 7th ed.
4. Boffetta P., Kaldor J.M. Secondary malignancies following cancer chemotherapy. Acta Oncol. 1994, 33:591-598.
5. Merlot A.M., Kalinowski D.S., Richardson D.R. Novel chelators for cancer treatment: where are we now?. Antioxid. Redox Signal. 2013, 18:973-1006.
6. Kolberg M., Strand K.R., Graff P., Andersson K.K. Structure, function, and mechanism of ribonucleotide reductases. Biochim. Biophys. Acta 2004, 1699:1-34.
7. Kalinowski D.S., Richardson D.R. The evolution of iron chelators for the treatment of iron overload disease and cancer. Pharmacol. Rev. 2005, 57:547-583.
8. Le N.T., Richardson D.R. Iron chelators with high antiproliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: a link between iron metabolism and proliferation. Blood 2004, 104:2967-2975.
9. Ellen T.P., Ke Q., Zhang P., Costa M. NDRG1, a growth and cancer related gene: regulation of gene expression and function in normal and disease states. Carcinogenesis 2008, 29:2-8.
10. Chen Z., Zhang D., Yue F., Zheng M., Kovacevic Z., Richardson D.R. The iron chelators Dp44mT and DFO inhibit TGF-β-induced epithelial-mesenchymal transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1). J. Biol. Chem. 2012, 287:17016-17028.
11. Kovacevic Z., Chikhani S., Lui G.Y., Sivagurunathan S., Richardson D.R. The iron-regulated metastasis suppressor NDRG1 targets NEDD4L, PTEN, and SMAD4 and inhibits the PI3K and Ras signaling pathways. Antioxid. Redox Signal. 2013, 18:874-887.
12. Mehlen P., Puisieux A. Metastasis: a question of life or death. Nat. Rev. Cancer 2006, 6:449-458.
13. Lawen A., Lane D.J.R. Mammalian iron homeostasis in health and disease: uptake, storage, transport, and molecular mechanisms of action. Antioxid. Redox Signal. 2013, 18:2473-2507.
14. Andrews N.C. Iron homeostasis: insights from genetics and animal models. Nat. Rev. Genet. 2000, 1:208-217.
15. Yu Y., Kovacevic Z., Richardson D.R. Tuning cell cycle regulation with an iron key. Cell Cycle 2007, 6:1982-1994.
16. Nyholm S., Mann G.J., Johansson A.G., Bergeron R.J., Graslund A., Thelander L. Role of ribonucleotide reductase in inhibition of mammalian cell growth by potent iron chelators. J. Biol. Chem. 1993, 268:26200-26205.
17. Richardson D.R., Kalinowski D.S., Lau S., Jansson P.J., Lovejoy D.B. Cancer cell iron metabolism and the development of potent iron chelators as anti-tumour agents. Biochim. Biophys. Acta 2009, 1790:702-717.
18. Lin Z.P., Belcourt M.F., Carbone R., Eaton J.S., Penketh P.G., Shadel G.S., Cory J.G., Sartorelli A.C. Excess ribonucleotide reductase R2 subunits coordinate the S phase checkpoint to facilitate DNA damage repair and recovery from replication stress. Biochem. Pharmacol. 2007, 73:760-772.
19. Tanaka H., Arakawa H., Yamaguchi T., Shiraishi K., Fukuda S., Matsui K., Takei Y., Nakamura Y. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature 2000, 404:42-49.
20. Le N.T., Richardson D.R. The role of iron in cell cycle progression and the proliferation of neoplastic cells. Biochim. Biophys. Acta 2002, 1603:31-46.
21. Guittet O., Hakansson P., Voevodskaya N., Fridd S., Graslund A., Arakawa H., Nakamura Y., Thelander L. Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in resting cells in response to DNA damage and in proliferating cells. J. Biol. Chem. 2001, 276:40647-40651.
22. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell 2000, 100:57-70.
23. Tsimberidou A.M., Alvarado Y., Giles F.J. Evolving role of ribonucleoside reductase inhibitors in hematologic malignancies. Expert Rev. Anticancer Ther. 2002, 2:437-448.
24. Cory J.G. Ribonucleotide reductase as a chemotherapeutic target. Adv. Enzyme Regul. 1988, 27:437-455.
25. Wang G., Miskimins R., Miskimins W.K. Mimosine arrests cells in G1 by enhancing the levels of p27(Kip1). Exp. Cell Res. 2000, 254:64-71.
26. Fukuchi K., Tomoyasu S., Watanabe H., Kaetsu S., Tsuruoka N., Gomi K. Iron deprivation results in an increase in p53 expression. Biol. Chem. Hoppe Seyler 1995, 376:627-630.
27. Kulp K.S., Green S.L., Vulliet P.R. Iron deprivation inhibits cyclin-dependent kinase activity and decreases cyclin D/CDK4 protein levels in asynchronous MDA-MB-453 human breast cancer cells. Exp. Cell Res. 1996, 229:60-68.
28. Lucas J.J., Szepesi A., Domenico J., Takase K., Tordai A., Terada N., Gelfand E.W. Effects of iron-depletion on cell cycle progression in normal human T lymphocytes: selective inhibition of the appearance of the cyclin A-associated component of the p33cdk2 kinase. Blood 1995, 86:2268-2280.
29. Vidal A., Koff A. Cell-cycle inhibitors: three families united by a common cause. Gene 2000, 247:1-15.
30. Nurtjahja-Tjendraputra E., Fu D., Phang J.M., Richardson D.R. Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency-mediated growth suppression. Blood 2007, 109:4045-4054.
31. Gao J., Richardson D.R. The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents, IV: the mechanisms involved in inhibiting cell cycle progression. Blood 2001, 98:842-850.
32. N. Defamie, A. Chepied, M. Mesnil, Connexins, gap junctions and tissue invasion, FEBS Lett. , (in press). http://dx.doi.org/10.1016/j.febslet.2014.01.012.
33. Weinberg R.A. The retinoblastoma protein and cell cycle control. Cell 1995, 81:323-330.
34. Halliwell B., Gutteridge J. Free Radicals in Biology and Medicine 1989, Claredon Press, Oxford.
35. Barnham K.J., Masters C.L., Bush A.I. Neurodegenerative diseases and oxidative stress. Nat. Rev. Drug Discov. 2004, 3:205-214.
36. Alper G., Narayanan V. Friedreich's ataxia. Pediatr. Neurol. 2003, 28:335-341.
37. Wong C., Richardson D.R. Beta-thalassaemia: emergence of new and improved iron chelators for treatment. Int. J. Biochem. Cell Biol. 2003, 35:1144-1149.
38. Lane D.J.R., Huang M.L., Ting S., Sivagurunathan S., Richardson D.R. Biochemistry of cardiomyopathy in the mitochondrial disease Friedreich's ataxia. Biochem. J. 2013, 453:321-336.
39. Chevion M. A site-specific mechanism for free radical induced biological damage: the essential role of redox-active transition metals. Free Radic. Biol. Med. 1988, 5:27-37.
40. Gorrini C., Harris I.S., Mak T.W. Modulation of oxidative stress as an anticancer strategy. Nat. Rev. Drug Discov. 2013, 12:931-947.
41. Yu Y., Kalinowski D.S., Kovacevic Z., Siafakas A.R., Jansson P.J., Stefani C., Lovejoy D.B., Sharpe P.C., Bernhardt P.V., Richardson D.R. Thiosemicarbazones from the old to new: iron chelators that are more than just ribonucleotide reductase inhibitors. J. Med. Chem. 2009, 52:5271-5294.
42. Richardson D.R. Molecular mechanisms of iron uptake by cells and the use of iron chelators for the treatment of cancer. Curr. Med. Chem. 2005, 12:2711-2729.
43. Baker E., Vitolo M.L., Webb J. Iron chelation by pyridoxal isonicotinoyl hydrazone and analogues in hepatocytes in culture. Biochem. Pharmacol. 1985, 34:3011-3017.
44. Baker E., Richardson D.R., Gross S., Ponka P. Evaluation of the iron chelation potential of hydrazones of pyridoxal, salicylaldehyde and 2-hydroxy-1-naphthylaldehyde using the hepatocyte in culture. Hepatology 1992, 15:492-501.
45. Bae D.H., Jansson P.J., Huang M.L., Kovacevic Z., Kalinowski D., Lee C.S., Sahni S., Richardson D.R. The role of NDRG1 in the pathology and potential treatment of human cancers. J. Clin. Pathol. 2013, 66:911-917.
46. Fang B.A., Kovacevic Z., Park K.C., Kalinowski D.S., Jansson P.J., Lane D.J., Sahni S., Richardson D.R. Molecular functions of the iron-regulated metastasis suppressor, NDRG1, and its potential as a molecular target for cancer therapy. Biochim. Biophys. Acta 2013, (Epub ahead of print). 10.1016/j.bbcan.2013.11.002.
47. Sun J., Zhang D., Bae D.H., Sahni S., Jansson P., Zheng Y., Zhao Q., Yue F., Zheng M., Kovacevic Z., Richardson D.R. Metastasis suppressor, NDRG1, mediates its activity through signaling pathways and molecular motors. Carcinogenesis 2013, 34:1943-1954.
48. Kovacevic Z., Richardson D.R. The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer. Carcinogenesis 2006, 27:2355-2366.
49. Karaczyn A., Ivanov S., Reynolds M., Zhitkovich A., Kasprzak K.S., Salnikow K. Ascorbate depletion mediates up-regulation of hypoxia-associated proteins by cell density and nickel. J. Cell. Biochem. 2006, 97:1025-1035.
50. Richardson D.R. Potential of iron chelators as effective antiproliferative agents. Can. J. Physiol. Pharmacol. 1997, 75:1164-1180.
51. Richardson D.R., Milnes K. The potential of iron chelators of the pyridoxal isonicotinoyl hydrazone class as effective antiproliferative agents II: the mechanism of action of ligands derived from salicylaldehyde benzoyl hydrazone and 2-hydroxy-1-naphthylaldehyde benzoyl hydrazone. Blood 1997, 89:3025-3038.
52. Valle P., Timeus F., Piglione M., Rosso P., di Montezemolo L.C., Crescenzio N., Marranca D., Ramenghi U. Effect of different exposures to desferrioxamine on neuroblastoma cell lines. Pediatr. Hematol. Oncol. 1995, 12:439-446.
53. Blatt J., Stitely S. Antineuroblastoma activity of desferoxamine in human cell lines. Cancer Res. 1987, 47:1749-1750.
54. Richardson D., Ponka P., Baker E. The effect of the iron(III) chelator, desferrioxamine, on iron and transferrin uptake by the human malignant melanoma cell. Cancer Res. 1994, 54:685-689.
55. Knox J.J., Hotte S.J., Kollmannsberger C., Winquist E., Fisher B., Eisenhauer E.A. Phase II study of triapine in patients with metastatic renal cell carcinoma: a trial of the National Cancer Institute of Canada Clinical Trials Group (NCIC IND.161). Invest. New Drugs 2007, 25:471-477.
56. Kunos C.A., Radivoyevitch T., Waggoner S., Debernardo R., Zanotti K., Resnick K., Fusco N., Adams R., Redline R., Faulhaber P., Dowlati A. Radiochemotherapy plus 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in advanced-stage cervical and vaginal cancers. Gynecol. Oncol. 2013, 130:75-80.
57. Mortazavi A., Ling Y., Martin L.K., Wei L., Phelps M.A., Liu Z., Harper E.J., Ivy S.P., Wu X., Zhou B.S., Liu X., Deam D., Monk J.P., Hicks W.J., Yen Y., Otterson G.A., Grever M.R., Bekaii-Saab T. A phase I study of prolonged infusion of triapine in combination with fixed dose rate gemcitabine in patients with advanced solid tumors. Invest. New Drugs 2013, 31:685-695.
58. Martin L.K., Grecula J., Jia G., Wei L., Yang X., Otterson G.A., Wu X., Harper E., Kefauver C., Zhou B.S., Yen Y., Bloomston M., Knopp M., Ivy S.P., Grever M., Bekaii-Saab T. A dose escalation and pharmacodynamic study of triapine and radiation in patients with locally advanced pancreas cancer. Int. J. Radiat. Oncol. Biol. Phys. 2012, 84:e475-e481.
59. Kunos C., Radivoyevitch T., Abdul-Karim F.W., Fanning J., Abulafia O., Bonebrake A.J., Usha L. Ribonucleotide reductase inhibition restores platinum-sensitivity in platinum-resistant ovarian cancer: a Gynecologic Oncology Group Study. J. Transl. Med. 2012, 10:79.
60. Chao J., Synold T.W., Morgan R.J., Kunos C., Longmate J., Lenz H.J., Lim D., Shibata S., Chung V., Stoller R.G., Belani C.P., Gandara D.R., McNamara M., Gitlitz B.J., Lau D.H., Ramalingam S.S., Davies A., Espinoza-Delgado I., Newman E.M., Yen Y. A phase I and pharmacokinetic study of oral 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in the treatment of advanced-stage solid cancers: a California Cancer Consortium Study. Cancer Chemother. Pharmacol. 2012, 69:835-843.
61. Kolesar J.M., Sachidanandam K., Schelman W.R., Eickhoff J., Holen K.D., Traynor A.M., Alberti D.B., Thomas J.P., Chitambar C.R., Wilding G., Antholine W.E. Cytotoxic evaluation of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP, in peripheral blood lymphocytes of patients with refractory solid tumors using electron paramagnetic resonance. Exp. Ther. Med. 2011, 2:119-123.
62. Kunos C.A., Radivoyevitch T., Pink J., Chiu S.M., Stefan T., Jacobberger J., Kinsella T.J. Ribonucleotide reductase inhibition enhances chemoradiosensitivity of human cervical cancers. Radiat. Res. 2010, 174:574-581.
63. Kolesar J., Brundage R.C., Pomplun M., Alberti D., Holen K., Traynor A., Ivy P., Wilding G. Population pharmacokinetics of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine(R)) in cancer patients. Cancer Chemother. Pharmacol. 2011, 67:393-400.
64. Kunos C.A., Waggoner S., von Gruenigen V., Eldermire E., Pink J., Dowlati A., Kinsella T.J. Phase I trial of pelvic radiation, weekly cisplatin, and 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) for locally advanced cervical cancer. Clin. Cancer Res. 2010, 16:1298-1306.
65. Choi B.S., Alberti D.B., Schelman W.R., Kolesar J.M., Thomas J.P., Marnocha R., Eickhoff J.C., Ivy S.P., Wilding G., Holen K.D. The maximum tolerated dose and biologic effects of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) in combination with irinotecan for patients with refractory solid tumors. Cancer Chemother. Pharmacol. 2010, 66:973-980.
66. Jansson P.J., Sharpe P.C., Bernhardt P.V., Richardson D.R. Novel thiosemicarbazones of the ApT and DpT series and their copper complexes: identification of pronounced redox activity and characterization of their antitumor activity. J. Med. Chem. 2010, 53:5759-5769.
67. Lovejoy D.B., Jansson P.J., Brunk U.T., Wong J., Ponka P., Richardson D.R. Antitumor activity of metal-chelating compound Dp44mT is mediated by formation of a redox-active copper complex that accumulates in lysosomes. Cancer Res. 2011, 71:5871-5880.
68. Yuan J., Lovejoy D.B., Richardson D.R. Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment. Blood 2004, 104:1450-1458.
69. Shao J., Zhou B., Di Bilio A.J., Zhu L., Wang T., Qi C., Shih J., Yen Y. A ferrous-triapine complex mediates formation of reactive oxygen species that inactivate human ribonucleotide reductase. Mol. Cancer Ther. 2006, 5:586-592.
70. Whitnall M., Howard J., Ponka P., Richardson D.R. A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics. Proc. Natl. Acad. Sci. U.S.A. 2006, 103:14901-14906.
71. Terman A., Kurz T. Lysosomal iron, iron chelation, and cell death. Antioxid. Redox Signal. 2013, 18:888-898.
72. Lovejoy D.B., Sharp D.M., Seebacher N., Obeidy P., Prichard T., Stefani C., Basha M.T., Sharpe P.C., Jansson P.J., Kalinowski D.S., Bernhardt P.V., Richardson D.R. Novel second-generation di-2-pyridylketone thiosemicarbazones show synergism with standard chemotherapeutics and demonstrate potent activity against lung cancer xenografts after oral and intravenous administration in vivo. J. Med. Chem. 2012, 55:7230-7244.
73. Kovacevic Z., Chikhani S., Lovejoy D.B., Richardson D.R. Novel thiosemicarbazone iron chelators induce up-regulation and phosphorylation of the metastasis suppressor N-myc down-stream regulated gene 1: a new strategy for the treatment of pancreatic cancer. Mol. Pharmacol. 2011, 80:598-609.
74. Yu Y., Suryo Rahmanto Y., Richardson D.R. Bp44mT: an orally active iron chelator of the thiosemicarbazone class with potent anti-tumour efficacy. Br. J. Pharmacol. 2012, 165:148-166.
75. Quach P., Gutierrez E., Basha M.T., Kalinowski D.S., Sharpe P.C., Lovejoy D.B., Bernhardt P.V., Jansson P.J., Richardson D.R. Methemoglobin formation by triapine, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT), and other anticancer thiosemicarbazones: identification of novel thiosemicarbazones and therapeutics that prevent this effect. Mol. Pharmacol. 2012, 82:105-114.
76. Sun J., Zhang D., Zheng Y., Zhao Q., Zheng M., Kovacevic Z., Richardson D.R. Targeting the metastasis suppressor, NDRG1, using novel iron chelators: regulation of stress fiber-mediated tumor cell migration via modulation of the ROCK1/pMLC2 signaling pathway. Mol. Pharmacol. 2013, 83:454-469.
77. Gorman A.M., Healy S.J., Jager R., Samali A. Stress management at the ER: regulators of ER stress-induced apoptosis. Pharmacol. Ther. 2012, 134:306-316.
78. Schroder M., Kaufman R.J. The mammalian unfolded protein response. Annu. Rev. Biochem. 2005, 74:739-789.
79. Braakman I., Bulleid N.J. Protein folding and modification in the mammalian endoplasmic reticulum. Annu. Rev. Biochem. 2011, 80:71-99.
80. Doyle K.M., Kennedy D., Gorman A.M., Gupta S., Healy S.J., Samali A. Unfolded proteins and endoplasmic reticulum stress in neurodegenerative disorders. J. Cell. Mol. Med. 2011, 15:2025-2039.
81. Huang M.L.-H., Sivagurunathan S., Ting S., Jansson P.J., Austin C.J., Kelly M., Semsarian C., Zhang D., Richardson D.R. Molecular and functional alterations in a mouse cardiac model of Friedreich ataxia: activation of the integrated stress response, eIF2α phosphorylation, and the induction of downstream targets. Am. J. Pathol. 2013, 183:745-757.
82. Vecchi C., Montosi G., Zhang K., Lamberti I., Duncan S.A., Kaufman R.J., Pietrangelo A. ER stress controls iron metabolism through induction of hepcidin. Science 2009, 325:877-880.
83. Schonthal A.H. Pharmacological targeting of endoplasmic reticulum stress signaling in cancer. Biochem. Pharmacol. 2013, 85:653-666.
84. Baird T.D., Wek R.C. Eukaryotic initiation factor 2 phosphorylation and translational control in metabolism. Adv. Nutr. Res. 2012, 3:307-321.
85. Sahni S., Bae D.-H., Lane D.J.R., Kalinowski D., Jansson P.J., Richardson D.R. The iron-regulated metastasis suppressor, N-myc downstream regulated gene 1 (NDRG1), suppresses the PERK-eIF2α axis and inhibits stress-induced autophagy in cancer cells. J. Biol. Chem. 2014, (In revision, November 2013).
86. Harding H.P., Zhang Y., Ron D. Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 1999, 397:271-274.
87. Jager R., Bertrand M.J., Gorman A.M., Vandenabeele P., Samali A. The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress. Biol. Cell 2012, 104:259-270.
88. Harding H.P., Zhang Y., Bertolotti A., Zeng H., Ron D. Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol. Cell 2000, 5:897-904.
89. Anderson P., Kedersha N. Stressful initiations. J. Cell Sci. 2002, 115:3227-3234.
90. Anderson P., Kedersha N. Stress granules: the Tao of RNA triage. Trends Biochem. Sci. 2008, 33:141-150.
91. Jiang H.Y., Wek S.A., McGrath B.C., Lu D., Hai T., Harding H.P., Wang X., Ron D., Cavener D.R., Wek R.C. Activating transcription factor 3 is integral to the eukaryotic initiation factor 2 kinase stress response. Mol. Cell Biol. 2004, 24:1365-1377.
92. Nishitoh H. CHOP is a multifunctional transcription factor in the ER stress response. J. Biochem. 2012, 151:217-219.
93. Marciniak S.J., Yun C.Y., Oyadomari S., Novoa I., Zhang Y., Jungreis R., Nagata K., Harding H.P., Ron D. CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev. 2004, 18:3066-3077.
94. Zinszner H., Kuroda M., Wang X., Batchvarova N., Lightfoot R.T., Remotti H., Stevens J.L., Ron D. CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Gene Dev. 1998, 12:982-995.
95. McCullough K.D., Martindale J.L., Klotz L.O., Aw T.Y., Holbrook N.J. Gadd153 sensitizes cells to endoplasmic reticulum stress by down-regulating Bcl2 and perturbing the cellular redox state. Mol. Cell Biol. 2001, 21:1249-1259.
96. Szegezdi E., Herbert K.R., Kavanagh E.T., Samali A., Gorman A.M. Nerve growth factor blocks thapsigargin-induced apoptosis at the level of the mitochondrion via regulation of Bim. J. Cell. Mol. Med. 2008, 12:2482-2496.
97. Li G., Mongillo M., Chin K.-T., Harding H., Ron D., Marks A.R., Tabas I. Role of ERO1-α-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J. Cell Biol. 2009, 186:783-792.
98. Yamaguchi H., Wang H.-G. CHOP is involved in endoplasmic reticulum stress-induced apoptosis by enhancing DR5 expression in human carcinoma cells. J. Biol. Chem. 2004, 279:45495-45502.
99. Yagi A., Hasegawa Y., Xiao H.Y., Haneda M., Kojima E., Nishikimi A., Hasegawa T., Shimokata K., Isobe K.I. GADD34 induces p53 phosphorylation and p21/WAF1 transcription. J. Cell. Biochem. 2003, 90:1242-1249.
100. Yan W., Frank C.L., Korth M.J., Sopher B.L., Novoa I., Ron D., Katze M.G. Control of PERK eIF2alpha kinase activity by the endoplasmic reticulum stress-induced molecular chaperone P58IPK. Proc. Natl. Acad. Sci. U.S.A. 2002, 99:15920-15925.
101. Rutkowski D.T., Kang S.W., Goodman A.G., Garrison J.L., Taunton J., Katze M.G., Kaufman R.J., Hegde R.S. The role of p58IPK in protecting the stressed endoplasmic reticulum. Mol. Biol. Cell 2007, 18:3681-3691.
102. Chen X., Shen J., Prywes R. The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the ER to the Golgi. J. Biol. Chem. 2002, 277:13045-13052.
103. Yoshida H., Okada T., Haze K., Yanagi H., Yura T., Negishi M., Mori K. ATF6 activated by proteolysis binds in the presence of NF-Y (CBF) directly to the cis-acting element responsible for the mammalian unfolded protein response. Mol. Cell Biol. 2000, 20:6755-6767.
104. Rao R.V., Peel A., Logvinova A., del Rio G., Hermel E., Yokota T., Goldsmith P.C., Ellerby L.M., Ellerby H.M., Bredesen D.E. Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett. 2002, 514:122-128.
105. Yoshida H., Matsui T., Yamamoto A., Okada T., Mori K. XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 2001, 107:881-891.
106. Lee A.H., Iwakoshi N.N., Glimcher L.H. XBP-1 regulates a subset of endoplasmic reticulum resident chaperone genes in the unfolded protein response. Mol. Cell Biol. 2003, 23:7448-7459.
107. Lin J.H., Li H., Zhang Y., Ron D., Walter P. Divergent effects of PERK and IRE1 signaling on cell viability. PloS ONE 2009, 4:e4170.
108. Urano F., Wang X., Bertolotti A., Zhang Y., Chung P., Harding H.P., Ron D. Coupling of stress in the ER to activation of JNK protein kinases by transmembrane protein kinase IRE1. Science 2000, 287:664-666.
109. Kim I., Shu C.W., Xu W., Shiau C.W., Grant D., Vasile S., Cosford N.D., Reed J.C. Chemical biology investigation of cell death pathways activated by endoplasmic reticulum stress reveals cytoprotective modulators of ASK1. J. Biol. Chem. 2009, 284:1593-1603.
110. Dhanasekaran D.N., Reddy E.P. JNK signaling in apoptosis. Oncogene 2008, 27:6245-6251.
111. Hu P., Han Z., Couvillon A.D., Kaufman R.J., Exton J.H. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol. Cell Biol. 2006, 26:3071-3084.
112. Hetz C., Bernasconi P., Fisher J., Lee A.H., Bassik M.C., Antonsson B., Brandt G.S., Iwakoshi N.N., Schinzel A., Glimcher L.H., Korsmeyer S.J. Proapoptotic BAX and BAK modulate the unfolded protein response by a direct interaction with IRE1alpha. Science 2006, 312:572-576.
113. Woehlbier U., Hetz C. Modulating stress responses by the UPRosome: a matter of life and death. Trends Biochem. Sci. 2011, 36:329-337.
114. Roybal C.N., Yang S., Sun C.W., Hurtado D., Vander Jagt D.L., Townes T.M., Abcouwer S.F. Homocysteine increases the expression of vascular endothelial growth factor by a mechanism involving endoplasmic reticulum stress and transcription factor ATF4. J. Biol. Chem. 2004, 279:14844-14852.
115. Romero-Ramirez L., Cao H., Nelson D., Hammond E., Lee A.H., Yoshida H., Mori K., Glimcher L.H., Denko N.C., Giaccia A.J., Le Q.T., Koong A.C. XBP1 is essential for survival under hypoxic conditions and is required for tumor growth. Cancer Res. 2004, 64:5943-5947.
116. Brewer J.W., Hendershot L.M., Sherr C.J., Diehl J.A. Mammalian unfolded protein response inhibits cyclin D1 translation and cell-cycle progression. Proc. Natl. Acad. Sci. U.S.A. 1999, 96:8505-8510.
117. Bourougaa K., Naski N., Boularan C., Mlynarczyk C., Candeias M.M., Marullo S., Fahraeus R. Endoplasmic reticulum stress induces G2 cell-cycle arrest via mRNA translation of the p53 isoform p53/47. Mol. Cell 2010, 38:78-88.
118. Boelens J., Lust S., Offner F., Bracke M.E., Vanhoecke B.W. Review. The endoplasmic reticulum: a target for new anticancer drugs. In Vivo 2007, 21:215-226.
119. Lin J.H., Li H., Yasumura D., Cohen H.R., Zhang C., Panning B., Shokat K.M., Lavail M.M., Walter P. IRE1 signaling affects cell fate during the unfolded protein response. Science 2007, 318:944-949.
120. Lane D.J., Saletta F., Suryo Rahmanto Y., Kovacevic Z., Richardson D.R. N-myc downstream regulated 1 (NDRG1) is regulated by eukaryotic initiation factor 3a (eIF3a) during cellular stress caused by iron depletion. PloS ONE 2013, 8:e57273.
121. Chiang A.C., Massague J. Molecular basis of metastasis. N. Engl. J. Med. 2008, 359:2814-2823.
122. Thiery J.P., Acloque H., Huang R.Y., Nieto M.A. Epithelial-mesenchymal transitions in development and disease. Cell 2009, 139:871-890.
123. Kalluri R., Weinberg R.A. The basics of epithelial-mesenchymal transition. J. Clin. Invest. 2009, 119:1420-1428.
124. Yang J., Weinberg R.A. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev. Cell 2008, 14:818-829.
125. Weber G.F. Molecular mechanisms of metastasis. Cancer Lett. 2008, 270:181-190.
126. Talmadge J.E., Fidler I.J. AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res. 2010, 70:5649-5669.
127. Ramaswamy S., Ross K.N., Lander E.S., Golub T.R. A molecular signature of metastasis in primary solid tumors. Nat. Genet. 2003, 33:49-54.
128. Liu W., Xing F., Iiizumi-Gairani M., Okuda H., Watabe M., Pai S.K., Pandey P.R., Hirota S., Kobayashi A., Mo Y.-Y., Fukuda K., Li Y., Watabe K. N-myc downstream regulated gene 1 modulates Wnt-β-catenin signalling and pleiotropically suppresses metastasis. EMBO Mol. Med. 2012, 4:93-108.
129. Mani S.A., Guo W., Liao M.J., Eaton E.N., Ayyanan A., Zhou A.Y., Brooks M., Reinhard F., Zhang C.C., Shipitsin M., Campbell L.L., Polyak K., Brisken C., Yang J., Weinberg R.A. The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 2008, 133:704-715.
130. Christiansen J.J., Rajasekaran A.K. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006, 66:8319-8326.
131. Kalluri R., Neilson E.G. Epithelial-mesenchymal transition and its implications for fibrosis. J. Clin. Invest. 2003, 112:1776-1784.
132. Kalluri R., Weinberg R.A. The basics of epithelial-mesenchymal transition. J. Clin. Invest. 2009, 119:1420-1428.
133. Brabletz T. To differentiate or not-routes towards metastasis. Nat. Rev. Cancer 2012, 12:425-436.
134. Brabletz T., Jung A., Spaderna S., Hlubek F., Kirchner T. Opinion: migrating cancer stem cells-an integrated concept of malignant tumour progression. Nat. Rev. Cancer 2005, 5:744-749.
135. de Herreros A.G., Peiro S., Nassour M., Savagner P. Snail family regulation and epithelial mesenchymal transitions in breast cancer progression. J. Mammary Gland Biol. Neoplasia 2010, 15:135-147.
136. Yamada S., Pokutta S., Drees F., Weis W.I., Nelson W.J. Deconstructing the cadherin-catenin-actin complex. Cell 2005, 123:889-901.
137. Collinet C., Lecuit T. Stability and dynamics of cell-cell junctions. Prog. Mol. Biol. Transl. Sci. 2013, 116:25-47.
138. Hartsock A., Nelson W.J. Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim. Biophys. Acta 2008, 1778:660-669.
139. Perl A.K., Wilgenbus P., Dahl U., Semb H., Christofori G. A causal role for E-cadherin in the transition from adenoma to carcinoma. Nature 1998, 392:190-193.
140. Reya T., Clevers H. Wnt signalling in stem cells and cancer. Nature 2005, 434:843-850.
141. Kimelman D., Xu W. Beta-catenin destruction complex: insights and questions from a structural perspective. Oncogene 2006, 25:7482-7491.
142. Brembeck F.H., Schwarz-Romond T., Bakkers J., Wilhelm S., Hammerschmidt M., Birchmeier W. Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions. Gene Dev. 2004, 18:2225-2230.
143. Jamieson C., Sharma M., Henderson B.R. Wnt signaling from membrane to nucleus: β-catenin caught in a loop. Int. J. Biochem. Cell Biol. 2012, 44:847-850.
144. MacDonald B.T., Tamai K., He X. Wnt/β-catenin signaling: components, mechanisms, and diseases. Dev. Cell 2009, 17:9-26.
145. Tetsu O., McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 1999, 398:422-426.
146. Polakis P., Hart M., Rubinfeld B. Defects in the regulation of beta-catenin in colorectal cancer. Adv. Exp. Med. Biol. 1999, 470:23-32.
147. Polakis P. Wnt signaling and cancer. Gene Dev. 2000, 14:1837-1851.
148. Kawanishi J., Kato J., Sasaki K., Fujii S., Watanabe N., Niitsu Y. Loss of E-cadherin-dependent cell-cell adhesion due to mutation of the beta-catenin gene in a human cancer cell line, HSC-39. Mol. Cell Biol. 1995, 15:1175-1181.
149. Batlle E., Sancho E., Franci C., Dominguez D., Monfar M., Baulida J., Garcia De Herreros A. The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells. Nat. Cell Biol. 2000, 2:84-89.
150. Bolos V., Peinado H., Perez-Moreno M.A., Fraga M.F., Esteller M., Cano A. The transcription factor Slug represses E-cadherin expression and induces epithelial to mesenchymal transitions: a comparison with Snail and E47 repressors. J. Cell Sci. 2003, 116:499-511.
151. Stemmer V., de Craene B., Berx G., Behrens J. Snail promotes Wnt target gene expression and interacts with beta-catenin. Oncogene 2008, 27:5075-5080.
152. Medici D., Hay E.D., Goodenough D.A. Cooperation between snail and LEF-1 transcription factors is essential for TGF-β1-induced epithelial-mesenchymal transition. Mol. Biol. Cell 2006, 17:1871-1879.
153. Peinado H., Quintanilla M., Cano A. Transforming growth factor β-1 induces snail transcription factor in epithelial cell lines: mechanisms for epithelial mesenchymal transitions. J. Biol. Chem. 2003, 278:21113-21123.
154. Choi J., Park S.Y., Joo C.K. Transforming growth factor-β1 represses E-cadherin production via slug expression in lens epithelial cells. Invest. Ophthalmol. Vis. Sci. 2007, 48:2708-2718.
155. De Craene B., van Roy F., Berx G. Unraveling signalling cascades for the Snail family of transcription factors. Cell. Signal. 2005, 17:535-547.
156. Padua D., Massague J. Roles of TGFβ in metastasis. Cell Res. 2009, 19:89-102.
157. Vincent T., Neve E.P., Johnson J.R., Kukalev A., Rojo F., Albanell J., Pietras K., Virtanen I., Philipson L., Leopold P.L., Crystal R.G., de Herreros A.G., Moustakas A., Pettersson R.F., Fuxe J. A SNAIL1-SMAD3/4 transcriptional repressor complex promotes TGF-beta mediated epithelial-mesenchymal transition. Nat. Cell Biol. 2009, 11:943-950.
158. Peiro S., Escriva M., Puig I., Barbera M.J., Dave N., Herranz N., Larriba M.J., Takkunen M., Franci C., Munoz A., Virtanen I., Baulida J., Garcia de Herreros A. Snail1 transcriptional repressor binds to its own promoter and controls its expression. Nucleic Acids Res. 2006, 34:2077-2084.
159. Julien S., Puig I., Caretti E., Bonaventure J., Nelles L., van Roy F., Dargemont C., de Herreros A.G., Bellacosa A., Larue L. Activation of NF-kappaB by Akt upregulates Snail expression and induces epithelium mesenchyme transition. Oncogene 2007, 26:7445-7456.
160. Solanas G., Porta-de-la-Riva M., Agusti C., Casagolda D., Sanchez-Aguilera F., Larriba M.J., Pons F., Peiro S., Escriva M., Munoz A., Dunach M., de Herreros A.G., Baulida J. E-cadherin controls beta-catenin and NF-kappaB transcriptional activity in mesenchymal gene expression. J. Cell Sci. 2008, 121:2224-2234.
161. Chua K.-N., Ma J., Thiery J.-P. Targeted therapies in control of EMT in carcinoma and fibrosis. Drug Discov. Today 2007, 4:261-267.
162. Zhou B.P., Deng J., Xia W., Xu J., Li Y.M., Gunduz M., Hung M.C. Dual regulation of Snail by GSK-3β-mediated phosphorylation in control of epithelial-mesenchymal transition. Nat. Cell Biol. 2004, 6:931-940.
163. Yang Z., Rayala S., Nguyen D., Vadlamudi R.K., Chen S., Kumar R. Pak1 phosphorylation of snail, a master regulator of epithelial-to-mesenchyme transition, modulates snail's subcellular localization and functions. Cancer Res. 2005, 65:3179-3184.
164. Wang S.P., Wang W.L., Chang Y.L., Wu C.T., Chao Y.C., Kao S.H., Yuan A., Lin C.W., Yang S.C., Chan W.K., Li K.C., Hong T.M., Yang P.C. p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug. Nat. Cell Biol. 2009, 11:694-704.
165. van Belzen N., Dinjens W.N., Diesveld M.P., Groen N.A., van der Made A.C., Nozawa Y., Vlietstra R., Trapman J., Bosman F.T. A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms. Lab. Invest. 1997, 77:85-92.
166. Bandyopadhyay S., Pai S.K., Gross S.C., Hirota S., Hosobe S., Miura K., Saito K., Commes T., Hayashi S., Watabe M., Watabe K. The Drg-1 gene suppresses tumor metastasis in prostate cancer. Cancer Res. 2003, 63:1731-1736.
167. Guan R.J., Ford H.L., Fu Y., Li Y., Shaw L.M., Pardee A.B. Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Cancer Res. 2000, 60:749-755.
168. Liu W., Iiizumi-Gairani M., Okuda H., Kobayashi A., Watabe M., Pai S.K., Pandey P.R., Xing F., Fukuda K., Modur V., Hirota S., Suzuki K., Chiba T., Endo M., Sugai T., Watabe K. KAI1 gene is engaged in NDRG1 gene-mediated metastasis suppression through the ATF3-NFkappaB complex in human prostate cancer. J. Biol. Chem. 2011, 286:18949-18959.
169. Wissing M., Rosmus N., Carducci M., Kachhap S. NDRG1 (N-myc downstream regulated 1). Atlas Genet. Cytogenet. Oncol. Haematol. 2009, http://AtlasGeneticsOncology.org/Genes/NDRG1ID41512ch8q24.html.
170. Zhang P., Tchou-Wong K.M., Costa M. Egr-1 mediates hypoxia-inducible transcription of the NDRG1 gene through an overlapping Egr-1/Sp1 binding site in the promoter. Cancer Res. 2007, 67:9125-9133.
171. Stein S., Thomas E.K., Herzog B., Westfall M.D., Rocheleau J.V., Jackson R.S., Wang M., Liang P. NDRG1 is necessary for p53-dependent apoptosis. J. Biol. Chem. 2004, 279:48930-48940.
172. Ulrix W., Swinnen J.V., Heyns W., Verhoeven G. The differentiation-related gene 1, Drg1, is markedly upregulated by androgens in LNCaP prostatic adenocarcinoma cells. FEBS Lett. 1999, 455:23-26.
173. Cangul H. Hypoxia upregulates the expression of the NDRG1 gene leading to its overexpression in various human cancers. BMC Genet. 2004, 5:27.
174. Ziello J.E., Jovin I.S., Huang Y. Hypoxia-inducible factor (HIF)-1 regulatory pathway and its potential for therapeutic intervention in malignancy and ischemia. Yale J. Biol. Med. 2007, 80:51-60.
175. Han Y.H., Xia L., Song L.P., Zheng Y., Chen W.L., Zhang L., Huang Y., Chen G.Q., Wang L.S. Comparative proteomic analysis of hypoxia-treated and untreated human leukemic U937 cells. Proteomics 2006, 6:3262-3274.
176. Semenza G.L. Hypoxia and cancer. Cancer Metastasis Rev. 2007, 26:223-224.
177. Wang G.L., Semenza G.L. Purification and characterization of hypoxia-inducible factor 1. J. Biol. Chem. 1995, 270:1230-1237.
178. Salnikow K., Kluz T., Costa M., Piquemal D., Demidenko Z.N., Xie K., Blagosklonny M.V. The regulation of hypoxic genes by calcium involves c-Jun/AP-1, which cooperates with hypoxia-inducible factor 1 in response to hypoxia. Mol. Cell Biol. 2002, 22:1734-1741.
179. Huang L.E. Carrot and stick: HIF-α engages c-Myc in hypoxic adaptation. Cell Death Differ. 2008, 15:672-677.
180. Shimono A., Okuda T., Kondoh H. N-myc-dependent repression of ndr1, a gene identified by direct subtraction of whole mouse embryo cDNAs between wild type and N-myc mutant. Mech. Dev. 1999, 83:39-52.
181. Zhou D., Salnikow K., Costa M. Cap43, a novel gene specifically induced by Ni2+ compounds. Cancer Res. 1998, 58:2182-2189.
182. Lai L.C., Su Y.Y., Chen K.C., Tsai M.H., Sher Y.P., Lu T.P., Lee C.Y., Chuang E.Y. Down-regulation of NDRG1 promotes migration of cancer cells during reoxygenation. PloS ONE 2011, 6:e24375.
183. Anderson P., Kedersha N. RNA granules. J. Cell Biol. 2006, 172:803-808.
184. Wang J., Cai J., Li Z., Hu S., Yu L., Xiao L., Wang Z. Expression and biological function of N-myc down-regulated gene 1 in human cervical cancer. J. Huazhong Univ. Sci. Technolog. Med. Sci. 2010, 30:771-776.
185. Dixon K.M., Lui G.Y., Kovacevic Z., Zhang D., Yao M., Chen Z., Dong Q., Assinder S.J., Richardson D.R. Dp44mT targets the AKT, TGF-beta and ERK pathways via the metastasis suppressor NDRG1 in normal prostate epithelial cells and prostate cancer cells. Br. J. Cancer 2013, 108:409-419.
186. Kim K.T., Ongusaha P.P., Hong Y.K., Kurdistani S.K., Nakamura M., Lu K.P., Lee S.W. Function of Drg1/Rit42 in p53-dependent mitotic spindle checkpoint. J. Biol. Chem. 2004, 279:38597-38602.
187. Kovacevic Z., Sivagurunathan S., Mangs H., Chikhani S., Zhang D., Richardson D.R. The metastasis suppressor, N-myc downstream regulated gene 1 (NDRG1), upregulates p21 via p53-independent mechanisms. Carcinogenesis 2011, 32:732-740.
188. Downward J. Targeting RAS signalling pathways in cancer therapy. Nat. Rev. Cancer 2003, 3:11-22.
189. Gomez-Casero E., Navarro M., Rodriguez-Puebla M.L., Larcher F., Paramio J.M., Conti C.J., Jorcano J.L. Regulation of the differentiation-related gene Drg-1 during mouse skin carcinogenesis. Mol. Carcinog. 2001, 32:100-109.
190. Li J., Kretzner L. The growth-inhibitory Ndrg1 gene is a Myc negative target in human neuroblastomas and other cell types with overexpressed N- or c-myc. Mol. Cell. Biochem. 2003, 250:91-105.
191. Kachhap S.K., Faith D., Qian D.Z., Shabbeer S., Galloway N.L., Pili R., Denmeade S.R., DeMarzo A.M., Carducci M.A. The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin. PloS ONE 2007, 2:e844.
192. Tojkander S., Gateva G., Schevzov G., Hotulainen P., Naumanen P., Martin C., Gunning P.W., Lappalainen P. A molecular pathway for myosin II recruitment to stress fibers. Curr. Biol. 2011, 21:539-550.
193. Fan Y.L., Zheng M., Tang Y.L., Liang X.H. A new perspective of vasculogenic mimicry: EMT and cancer stem cells (Review). Oncol. Lett. 2013, 6:1174-1180.