The iron chelators Dp44mT and DFO inhibit TGF-β-induced epithelial-mesenchymal transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1)

Journal of Biological Chemistry

Volumn 287, Issue 21, 2012, Pages 17016-17028

  Chen, Zhiqiang ^a,b   Zhang, Daohai ^b   Yue, Fei ^a   Zheng, Minhua ^a   Kovacevic, Zaklina ^b   Richardson, Des R ^a,b  

^a SHANGHAI JIAO TONG UNIVERSITY SCHOOL OF MEDICINE   (China)

^b UNIVERSITY OF SYDNEY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ANTI-TUMOR ACTIVITIES; CANCER CELLS; DESFERRIOXAMINE; E-CADHERINS; EPITHELIAL-MESENCHYMAL TRANSITION; HYPOXIA-INDUCIBLE FACTOR 1; IRON CHELATORS; IRON DEPLETION; MORPHOLOGICAL CHANGES; OVER-EXPRESSION; RICHARDSON; STABLE CLONES; STIMULATED CELLS; THIOSEMICARBAZONES; TRANSFORMING GROWTH FACTORS; UP-REGULATION; WNT PATHWAY;

CELL MEMBRANES; CLONE CELLS; CYTOLOGY; GENES; GLYCOPROTEINS; IRON; PATHOLOGY;

CHELATION;

BETA CATENIN; DEFEROXAMINE; DI 2 PYRIDYLKETONE 4,4 DIMETHYL 3 THIOSEMICARBAZONE; OCCLUDIN; PROTEIN ZO1; SMAD PROTEIN; TRANSCRIPTION FACTOR SLUG; TRANSCRIPTION FACTOR SNAIL; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG; UVOMORULIN; WNT PROTEIN;

ARTICLE; CELL INVASION; CELL MIGRATION; CONTROLLED STUDY; DRUG MECHANISM; DRUG STRUCTURE; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; HUMAN CELL; MALE; N MYC DOWNSTREAM REGULATED GENE 1; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE;

BETA CATENIN; CADHERINS; CELL CYCLE PROTEINS; CELL LINE, TUMOR; DEFEROXAMINE; EPITHELIAL-MESENCHYMAL TRANSITION; GENE KNOCKDOWN TECHNIQUES; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; PROTO-ONCOGENE PROTEINS C-MYC; SIDEROPHORES; SMAD PROTEINS; THIOSEMICARBAZONES; TRANSFORMING GROWTH FACTOR BETA1; UP-REGULATION; WNT SIGNALING PATHWAY;

EID: 84861212961     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.350470     Document Type: Article

References (51)

1. Kalinowski, D. S., and Richardson, D. R. (2005) The evolution of iron chelators for the treatment of iron overload disease and cancer. Pharmacol. Rev. 57, 547-583 (Pubitemid 43036441)
2. Miller, L. D., Coffman, L. G., Chou, J. W., Black, M. A., Bergh, J., D'Agostino, R., Jr., Torti, S. V., and Torti, F. M. An iron regulatory gene signature predicts outcome in breast cancer. Cancer Res. 71, 6728-6737
3. Thiery, J. P., Acloque, H., Huang, R. Y., and Nieto, M. A. (2009) Epithelial-mesenchymal transitions in development and disease. Cell 139, 871-890
4. Christiansen, J. J., and Rajasekaran, A. K. (2006) Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 66, 8319-8326 (Pubitemid 44449137)
5. Kalluri, R., and Weinberg, R. A. (2009) The basics of epithelial-mesenchymal transition. J. Clin. Invest. 119, 1420-1428
6. Miettinen, P. J., Ebner, R., Lopez, A. R., and Derynck, R. (1994) TGF-βinduced transdifferentiation of mammary epithelial cells to mesenchymal cells: involvement of type I receptors. J. Cell Biol. 127, 2021-2036
7. Zavadil, J., and Böttinger, E. P. (2005) TGF-β and epithelial-to-mesenchymal transitions. Oncogene 24, 5764-5774
8. Oft, M., Heider, K. H., and Beug, H. (1998) TGFβ signaling is necessary for carcinoma cell invasiveness and metastasis. Curr. Biol. 8, 1243-1252 (Pubitemid 28540052)
9. Pardali, K., and Moustakas, A. (2007) Actions of TGF-β as tumor suppressor and pro-metastatic factor in human cancer. Biochim. Biophys. Acta 1775, 21-62 (Pubitemid 44881193)
10. Rao, V. A., Klein, S. R., Agama, K. K., Toyoda, E., Adachi, N., Pommier, Y., and Shacter, E. B. (2009) The iron chelator Dp44mT causes DNA damage and selective inhibition of topoisomerase IIα in breast cancer cells. Cancer Res. 69, 948-957
11. Le, N. T., and Richardson, D. R. (2004) 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 104, 2967-2975 (Pubitemid 39434989)
12. Whitnall, M., Howard, J., Ponka, P., and Richardson, D. R. (2006) 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. 103, 14901-14906 (Pubitemid 44527826)
13. Richardson, D. R. (2005) Molecular mechanisms of iron uptake by cells and the use of iron chelators for the treatment of cancer. Curr. Med. Chem. 12, 2711-2729
14. Liang, S. X., and Richardson, D. R. (2003) The effect of potent iron chelators on the regulation of p53: examination of the expression, localization, and DNA binding activity of p53 and the transactivation of WAF1. Carcinogenesis 24, 1601-1614 (Pubitemid 37304665)
15. Nurtjahja-Tjendraputra, E., Fu, D., Phang, J. M., and Richardson, D. R. (2007) Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency-mediated growth suppression. Blood 109, 4045-4054 (Pubitemid 46641760)
16. Fu, D., and Richardson, D. R. (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. Blood 110, 752-761 (Pubitemid 47105414)
17. Richardson, D. R., Sharpe, P. C., Lovejoy, D. B., Senaratne, D., Kalinowski, D. S., Islam, M., and Bernhardt, P. V. (2006) Dipyridyl thiosemicarbazone chelators with potent and selective antitumor activity form iron complexes with redox activity. J. Med. Chem. 49, 6510-6521 (Pubitemid 44657445)
18. Lovejoy, D. B., Jansson, P. J., Brunk, U. T., Wong, J., Ponka, P., and Richardson, D. R. (2011) Antitumor activity of metal-chelating compound Dp44mT is mediated by formation of a redox-active copper complex that accumulates in lysosomes. Cancer Res. 71, 5871-5880
19. Yu, Y., Suryo Rahmanto, Y., Hawkins, C. L., and Richardson, D. R. (2011) The potent and novel thiosemicarbazone chelators di-2-pyridylketone-4,4- dimethyl-3-thiosemicarbazone and 2-benzoylpyridine-4,4-dimethyl-3- thiosemicarbazone affect crucial thiol systems required for ribonucleotide reductase activity. Mol. Pharmacol. 79, 921-931
20. Kovacevic, Z., Fu, D., and Richardson, D. R. (2008) The iron-regulated metastasis suppressor, Ndrg-1: identification of novel molecular targets. Biochim. Biophys. Acta 1783, 1981-1992
21. Bandyopadhyay, S., Pai, S. K., Gross, S. C., Hirota, S., Hosobe, S., Miura, K., Saito, K., Commes, T., Hayashi, S., Watabe, M., and Watabe, K. (2003) The Drg-1 gene suppresses tumor metastasis in prostate cancer. Cancer Res. 63, 1731-1736 (Pubitemid 36460828)
22. Guan, R. J., Ford, H. L., Fu, Y., Li, Y., Shaw, L. M., and Pardee, A. B. (2000) Drg-1 as a differentiation-related, putative metastatic suppressor gene in human colon cancer. Cancer Res. 60, 749-755 (Pubitemid 30094577)
23. Bandyopadhyay, S., Pai, S. K., Hirota, S., Hosobe, S., Takano, Y., Saito, K., Piquemal, D., Commes, T., Watabe, M., Gross, S. C., Wang, Y., Ran, S., and Watabe, K. (2004) Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression. Oncogene 23, 5675-5681 (Pubitemid 39093045)
24. Maruyama, Y., Ono, M., Kawahara, A., Yokoyama, T., Basaki, Y., Kage, M., Aoyagi, S., Kinoshita, H., and Kuwano, M. (2006) Tumor growth suppression in pancreatic cancer by a putative metastasis suppressor gene Cap43/NDRG1/Drg-1 through modulation of angiogenesis. Cancer Res. 66, 6233-6242
25. Cangul, H. (2004) Hypoxia up-regulates the expression of the NDRG1 gene leading to its overexpression in various human cancers. BMC Genet. 5, 27
26. Ellen, T. P., Ke, Q., Zhang, P., and Costa, M. (2008) NDRG1, a growth and cancer-related gene: regulation of gene expression and function in normal and disease states. Carcinogenesis 29, 2-8 (Pubitemid 351201735)
27. Shah, M. A., Kemeny, N., Hummer, A., Drobnjak, M., Motwani, M., Cordon-Cardo, C., Gonen, M., and Schwartz, G. K. (2005) Drg1 expression in 131 colorectal liver metastases: correlation with clinical variables and patient outcomes. Clin. Cancer Res. 11, 3296-3302 (Pubitemid 40627878)
28. Kovacevic, Z., Chikhani, S., Lovejoy, D. B., and Richardson, D. R. (2011) Novel thiosemicarbazone iron chelators induce up-regulation and phosphorylation of the metastasis suppressor N-Myc downstream-regulated gene 1: a new strategy for the treatment of pancreatic cancer. Mol. Pharmacol. 80, 598-609
29. Yuan, J., Lovejoy, D. B., and Richardson, D. R. (2004) Novel di-2-pyridyl-derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment. Blood 104, 1450-1458 (Pubitemid 39166524)
30. Richardson, D., Ponka, P., and Baker, E. (1994) The effect of the iron(III) chelator, desferrioxamine, on iron and transferrin uptake by the human malignant melanoma cell. Cancer Res. 54, 685-689 (Pubitemid 24068323)
31. Bambang, I. F., Lu, D., Li, H., Chiu, L. L., Lau, Q. C., Koay, E., and Zhang, D. (2009) Cytokeratin 19 regulates endoplasmic reticulum stress and inhibits ERp29 expression via p38 MAPK/XBP-1 signaling in breast cancer cells. Exp. Cell Res. 315, 1964-1974
32. Pino, M. S., Kikuchi, H., Zeng, M., Herraiz, M. T., Sperduti, I., Berger, D., Park, D. Y., Iafrate, A. J., Zukerberg, L. R., and Chung, D. C. (2010) Epithelial to mesenchymal transition is impaired in colon cancer cells with microsatellite instability. Gastroenterology 138, 1406-1417
33. Ellenrieder, V., Hendler, S. F., Boeck, W., Seufferlein, T., Menke, A., Ruhland, C., Adler, G., and Gress, T. M. (2001) Transforming growth factorß1 treatment leads to an epithelial-mesenchymal transdifferentiation of pancreatic cancer cells requiring extracellular signal-regulated kinase 2 activation. Cancer Res. 61, 4222-4228 (Pubitemid 32720992)
34. Wijnhoven, B. P., Dinjens, W. N., and Pignatelli, M. (2000) E-cadherin-catenin cell-cell adhesion complex and human cancer. Br J. Surg. 87, 992-1005 (Pubitemid 30496847)
35. Salnikow, K., Davidson, T., Zhang, Q., Chen, L. C., Su, W., and Costa, M. (2003) The involvement of hypoxia-inducible transcription factor-1-dependent pathway in nickel carcinogenesis. Cancer Res. 63, 3524-3530 (Pubitemid 36793031)
36. Kovacevic, Z., Sivagurunathan, S., Mangs, H., Chikhani, S., Zhang, D., and Richardson, D. R. (2011) The metastasis suppressor, N-Myc downstream-regulated gene 1 (NDRG1), up-regulates p21 via p53-independent mechanisms. Carcinogenesis 32, 732-740
37. Sugiki, T., Murakami, M., Taketomi, Y., Kikuchi-Yanoshita, R., and Kudo, I. (2004) N-Myc down-regulated gene 1 is a phosphorylated protein in mast cells. Biol. Pharm. Bull. 27, 624-627 (Pubitemid 41694660)
38. van Belzen, N., Dinjens, W. N., Diesveld, M. P., Groen, N. A., van der Made, A. C., Nozawa, Y., Vlietstra, R., Trapman, J., and Bosman, F. T. (1997) A novel gene which is up-regulated during colon epithelial cell differentiation and down-regulated in colorectal neoplasms. Lab. Invest. 77, 85-92 (Pubitemid 27328362)
39. Bandyopadhyay, S., Pai, S. K., Hirota, S., Hosobe, S., Tsukada, T., Miura, K., Takano, Y., Saito, K., Commes, T., Piquemal, D., Watabe, M., Gross, S., Wang, Y., Huggenvik, J., and Watabe, K. (2004) PTEN up-regulates the tumor metastasis suppressor gene Drg-1 in prostate and breast cancer. Cancer Res. 64, 7655-7660 (Pubitemid 39446890)
40. Behrens, J., von Kries, J. P., Kühl, M., Bruhn, L., Wedlich, D., Grosschedl, R., and Birchmeier, W. (1996) Functional interaction of β-catenin with the transcription factor LEF-1. Nature 382, 638-642 (Pubitemid 26268958)
41. Suzuki, H., Masuda, N., Shimura, T., Araki, K., Kobayashi, T., Tsutsumi, S., Asao, T., and Kuwano, H. (2008) Nuclear β-catenin expression at the invasive front and in the vessels predicts liver metastasis in colorectal carcinoma. Anticancer Res. 28, 1821-1830 (Pubitemid 351892891)
42. Elston, M. S., Gill, A. J., Conaglen, J. V., Clarkson, A., Cook, R. J., Little, N. S., Robinson, B. G., Clifton-Bligh, R. J., and McDonald, K. L. (2009) Nuclear accumulation of e-cadherin correlates with loss of cytoplasmic membrane staining and invasion in pituitary adenomas. J. Clin. Endocrinol. Metab. 94, 1436-1442
43. Céspedes, M. V., Larriba, M. J., Pavón, M. A., Alamo, P., Casanova, I., Parreño, M., Feliu, A., Sancho, F. J., Muñoz, A., and Mangues, R. (2010) Site-dependent E-cadherin cleavage and nuclear translocation in a metastatic colorectal cancer model. Am. J. Pathol. 177, 2067-2079
44. Hartsock, A., and Nelson, W. J. (2008) Adherens and tight junctions: structure, function, and connections to the actin cytoskeleton. Biochim. Biophys. Acta 1778, 660-669 (Pubitemid 351317795)
45. Hotz, B., Arndt, M., Dullat, S., Bhargava, S., Buhr, H. J., and Hotz, H. G. (2007) Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer. Clin. Cancer Res. 13, 4769-4776 (Pubitemid 47294783)
46. Heldin, C. H., Miyazono, K., and ten Dijke, P. (1997) TGF-β signaling from cell membrane to nucleus through SMAD proteins. Nature 390, 465-471 (Pubitemid 28013118)
47. Kachhap, S. K., Faith, D., Qian, D. Z., Shabbeer, S., Galloway, N. L., Pili, R., Denmeade, S. R., DeMarzo, A. M., and Carducci, M. A. (2007) The N-Myc down-regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin. PLoS One 2, e844
48. Wu, D., and Pan, W. (2010) GSK3: a multifaceted kinase in Wnt signaling. Trends Biochem. Sci. 35, 161-168
49. Reya, T., and Clevers, H. (2005) Wnt signaling in stem cells and cancer. Nature 434, 843-850 (Pubitemid 40558990)
50. Sherr, C. J. (1994) G1 phase progression: cycling on cue. Cell 79, 551-555
51. Brandl, M., Seidler, B., Haller, F., Adamski, J., Schmid, R. M., Saur, D., and Schneider, G. (2010) IKK(α) controls canonical TGF(β)-SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in panc1 cells. J. Cell Sci. 123, 4231-4239