The iron-regulated metastasis suppressor NDRG1 targets NEDD4L, PTEN, and SMAD4 and inhibits the PI3K and ras signaling pathways

Antioxidants and Redox Signaling

Volumn 18, Issue 8, 2013, Pages 874-887

  Kovacevic, Zaklina ^a   Chikhani, Sherin ^a   Lui, Goldie Y L ^a   Sivagurunathan, Sutharshani ^a   Richardson, Des R ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

DI 2 PYRIDYLKETONE 4 CYCLOHEXYL 4 METHYL 3 THIOSEMICARBAZONE HYDROCHLORIDE; DI 2 PYRIDYLKETONE 4,4 DIMETHYL 3 THIOSEMICARBAZONE; GLI SIMILAR 3; IRON CHELATING AGENT; NEURAL PRECURSOR CELL EXPRESSED DEVELOPMENTALLY DOWNREGULATED 4 LIKE; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; RAS PROTEIN; SMAD4 PROTEIN; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR BETA; TUMOR SUPPRESSOR PROTEIN; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CARCINOGENESIS; CONTROLLED STUDY; DRUG TARGETING; ENZYME INHIBITION; FEMALE; GENE CONTROL; GENE EXPRESSION REGULATION; GENE FUNCTION; GENE OVEREXPRESSION; GENE SILENCING; HUMAN; HUMAN CELL; IRON DEPLETION; METASTASIS INHIBITION; METASTASIS SUPPRESSOR GENE; MICROARRAY ANALYSIS; MOUSE; N MYC DOWNSTREAM REGULATED GENE 1; NONHUMAN; NUCLEOTIDE SEQUENCE; PANCREAS CANCER; PRIORITY JOURNAL; PROTEIN INDUCTION; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE; UPREGULATION;

CELL CYCLE PROTEINS; CELL LINE, TUMOR; ENDOSOMAL SORTING COMPLEXES REQUIRED FOR TRANSPORT; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; IRON; PANCREATIC NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; PROTEIN BINDING; PROTO-ONCOGENE PROTEINS P21(RAS); PTEN PHOSPHOHYDROLASE; SIGNAL TRANSDUCTION; SMAD4 PROTEIN; UBIQUITIN-PROTEIN LIGASES;

EID: 84873882079     PISSN: 15230864     EISSN: 15577716     Source Type: Journal    
DOI: 10.1089/ars.2011.4273     Document Type: Article

References (50)

1. Angst E, Sibold S, Tiffon C, Weimann R, Gloor B, Candinas D, and Stroka D. Cellular differentiation determines the expression of the hypoxia-inducible protein NDRG1 in pancreatic cancer. Br J Cancer 95: 307-313, 2006.
2. Bandyopadhyay S, Pai SK, Gross SC, Hirota S, Hosobe S, Miura K, Saito K, Commes T, Hayashi S, Watabe M, and Watabe K. The Drg-1 gene suppresses tumor metastasis in prostate cancer. Cancer Res 63: 1731-1736, 2003.
3. Bandyopadhyay S, Pai SK, Hirota S, Hosobe S, Takano Y, Saito K, Piquemal D, Commes T, Watabe M, Gross SC, Wang Y, Ran S, and Watabe K. Role of the putative tumor metastasis suppressor gene Drg-1 in breast cancer progression. Oncogene 23: 5675-5681, 2004.
4. Burris H, 3rd and Rocha-Lima C. New therapeutic directions for advanced pancreatic cancer: targeting the epidermal growth factor and vascular endothelial growth factor pathways. Oncologist 13: 289-298, 2008.
5. Chalhoub N and Baker SJ. PTEN and the PI3-kinase pathway in cancer. Annu Rev Pathol 4: 127-150, 2009.
6. Chen H, Ross CA, Wang N, Huo Y, MacKinnon DF, Potash JB, Simpson SG, McMahon FJ, DePaulo Jr., JR, and McInnis MG. NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a homologue of the mouse Nedd4-2 gene. Eur J Hum Genet 9: 922-930, 2001.
7. Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK, and Testa Jr. Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tu-morigenicity by antisense RNA. Proc Natl Acad Sci USA 93: 3636-3641, 1996.
8. Chow JY, Ban M, Wu HL, Nguyen F, Huang M, Chung H, Dong H, and Carethers JM. TGF-beta downregulates PTEN via activation of NF-kappaB in pancreatic cancer cells. Am J Physiol Gastrointest Liver Physiol 298: G275-G282, 2010.
9. Chow JY, Cabral JA, Chang J, and Carethers JM. TGFbeta modulates PTEN expression independently of SMAD signaling for growth proliferation in colon cancer cells. Cancer Biol Ther 7: 1694-1699, 2008.
10. Chow JY, Dong H, Quach KT, Van Nguyen PN, Chen K, and Carethers JM. TGF-beta mediates PTEN suppression and cell motility through calcium-dependent PKC-alpha activation in pancreatic cancer cells. Am J Physiol Gastrointest Liver Physiol 294: G899-G905, 2008.
11. Chow JY, Quach KT, Cabrera BL, Cabral JA, Beck SE, and Carethers JM. RAS/ERK modulates TGFbeta-regulated PTEN expression in human pancreatic adenocarcinoma cells. Carcinogenesis 28: 2321-2327, 2007.
12. Dong Z, Arnold RJ, Yang Y, Park MH, Hrncirova P, Mechref Y, Novotny MV, and Zhang JT. Modulation of differentiation-related gene 1 expression by cell cycle blocker mimo-sine, revealed by proteomic analysis. Mol Cell Proteomics 4: 993-1001, 2005.
13. Ellen T, Ke Q, Zhang P, and Costa M. NDRG1, a growth and cancer related gene: regulation of gene expression and function in normal and disease states. Carcinogenesis 29: 2-8, 2007.
14. Ellenrieder V. TGFbeta regulated gene expression by Smads and Sp1/KLF-like transcription factors in cancer. Anticancer Res 28: 1531-1539, 2008.
15. Gao S, Alarcon C, Sapkota G, Rahman S, Chen PY, Goerner N, Macias MJ, Erdjument-Bromage H, Tempst P, and Massague J. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling. Mol Cell 36: 457-468, 2009.
16. Geissmann F, Prost C, Monnet JP, Dy M, Brousse N, and Hermine O. Transforming growth factor beta1, in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells. J Exp Med 187: 961-966, 1998.
17. Gysin S, Rickert P, Kastury K, and McMahon M. Analysis of genomic DNA alterations and mRNA expression patterns in a panel of human pancreatic cancer cell lines. Genes Chromosomes Cancer 44: 37-51, 2005.
18. Hahn SA, Hoque AT, Moskaluk CA, da Costa LT, Schutte M, Rozenblum E, Seymour AB, Weinstein CL, Yeo CJ, Hruban RH, and Kern SE. Homozygous deletion map at 18q21.1 in pancreatic cancer. Cancer Res 56: 490-494, 1996.
19. Hahn SA, Schutte M, Hoque AT, Moskaluk CA, da Costa LT, Rozenblum E, Weinstein CL, Fischer A, Yeo CJ, Hruban RH, and Kern SE. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 271: 350-353, 1996.
20. He J, de la Monte S, and Wands Jr. The p85beta regulatory subunit of PI3K serves as a substrate for PTEN protein phosphatase activity during insulin mediated signaling. Biochem Biophys Res Commun 397: 513-519, 2010.
21. Holm S. A simple sequentially rejective multiple test procedure. Scand J Stat 6: 65-70, 1979.
22. Hosoi F, Izumi H, Kawahara A, Murakami Y, Kinoshita H, Kage M, Nishio K, Kohno K, Kuwano M, and Ono M. N-myc downstream regulated gene 1/Cap43 suppresses tumor growth and angiogenesis of pancreatic cancer through attenuation of inhibitor of kappaB kinase beta expression. Cancer Res 69: 4983-4991, 2009.
23. Hu XY, Xu YM, Fu Q, Yu JJ, and Huang J. Nedd4L expression is downregulated in prostate cancer compared to benign prostatic hyperplasia. Eur J Surg Oncol 35: 527-531, 2009.
24. Ingham RJ, Gish G, and Pawson T. The Nedd4 family of E3 ubiquitin ligases: functional diversity within a common modular architecture. Oncogene 23: 1972-1984, 2004.
25. Jiang BH and Liu LZ. PI3K/PTEN signaling in angiogenesis and tumorigenesis. Adv Cancer Res 102: 19-65, 2009.
26. Kim YS, Nakanishi G, Lewandoski M, and Jetten AM. GLIS3, a novel member of the GLIS subfamily of Kruppel-like zinc finger proteins with repressor and activation functions. Nucleic Acids Res 31: 5513-5525, 2003.
27. Kovacevic Z, Chikhani S, Lovejoy DB, and Richardson DR. Novel thiosemicarbazone iron chelators induce up-regula-tion and phosphorylation of the metastasis suppressor, NDRG1: A new strategy for the treatment of pancreatic cancer. Mol Pharmacol 80: 598-609, 2011.
28. Kovacevic Z and Richardson DR. The metastasis suppressor, Ndrg-1: a new ally in the fight against cancer. Carcinogenesis 6: 1982-1994, 2006.
29. Kovacevic Z, Sivagurunathan S, Mangs H, Chikhani S, Zhang D, and Richardson DR. The metastasis suppressor, N-myc downstream regulated gene 1 (NDRG1), upregulates p21 via p53-independent mechanisms. Carcinogenesis 32: 732-740, 2011.
30. Kretzschmar M, Doody J, Timokhina I, and Massague J. A mechanism of repression of TGFbeta/Smad signaling by oncogenic Ras. Genes Dev 13: 804-816, 1999.
31. Lachat P, Shaw P, Gebhard S, van Belzen N, Chaubert P, and Bosman FT. Expression of NDRG1, a differentiation-related gene, in human tissues. Histochem Cell Biol 118: 399-408, 2002.
32. Laghi L, Orbetegli O, Bianchi P, Zerbi A, Di Carlo V, Boland CR, and Malesci A. Common occurrence of multiple K-RAS mutations in pancreatic cancers with associated precursor lesions and in biliary cancers. Oncogene 21: 4301-4306, 2002.
33. Le NT and Richardson DR. Iron chelators with high anti-proliferative activity up-regulate the expression of a growth inhibitory and metastasis suppressor gene: a link between iron metabolism and proliferation. Blood 104: 2967-2975, 2004.
34. Levy L and Hill CS. Smad4 dependency defines two classes of transforming growth factor b (TGF-b) target genes and distinguishes TGF-b-induced epithelial-mesenchymal transition from its antiproliferative and migratory responses. Mol Cell Biol 25: 8108-8125, 2005.
35. Maehama T and Dixon JE. The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3, 4, 5-trisphosphate. J Biol Chem 273: 13375-13378, 1998.
36. Maruyama Y, Ono M, Kawahara A, Yokoyama T, Basaki Y, Kage M, Aoyagi S, Kinoshita H, and Kuwano M. 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, 2006.
37. Massague J. TGF-beta signal transduction. Annu Rev Biochem 67: 753-791, 1998.
38. Murakami Y, Hosoi F, Izumi H, Maruyama Y, Ureshino H, Watari K, Kohno K, Kuwano M, and Ono M. Identification of sites subjected to serine/threonine phosphorylation by SGK1 affecting N-myc downstream-regulated gene 1 (NDRG1)/Cap43-dependent suppression of angiogenic CXC chemokine expression in human pancreatic cancer cells. Bio-chem Biophys Res Commun 396: 376-381, 2010.
39. Murray JT, Campbell DG, Morrice N, Auld GC, Shpiro N, Marquez R, Peggie M, Bain J, Bloomberg GB, Grahammer F, Lang F, Wulff P, Kuhl D, and Cohen P. Exploitation of KESTREL to identify NDRG family members as physiological substrates for SGK1 and GSK3. Biochem J 384: 477-488, 2004.
40. Simeone DM, Pham T, and Logsdon CD. Disruption of TGFbeta signaling pathways in human pancreatic cancer cells. Ann Surg 232: 73-80, 2000.
41. Smyth GK. Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat Appl Genet Mol Biol 3: Article3, 2004.
42. Stathopoulos GP, Androulakis N, Souglakos J, Stathopoulos J, and Georgoulias V. Present treatment and future expectations in advanced pancreatic cancer. Anticancer Res 28: 1303-1308, 2008.
43. Steelman LS, Stadelman KM, Chappell WH, Horn S, Basecke J, Cervello M, Nicoletti F, Libra M, Stivala F, Martelli AM, and McCubrey JA. Akt as a therapeutic target in cancer. Expert Opin Ther Targets 12: 1139-1165, 2008.
44. Subramanian G, Schwarz RE, Higgins L, McEnroe G, Chakravarty S, Dugar S, and Reiss M. Targeting endogenous transforming growth factor beta receptor signaling in SMAD4-deficient human pancreatic carcinoma cells inhibits their invasive phenotype1. Cancer Res 64: 5200-5211, 2004.
45. Taplick J, Kurtev V, Kroboth K, Posch M, Lechner T, and Seiser C. Homo-oligomerisation and nuclear localisation of mouse histone deacetylase 1. J Mol Biol 308: 27-38, 2001.
46. Venkatasubbarao K, Ahmed MM, Mohiuddin M, Swiderski C, Lee E, Gower WR, Jr., Salhab KF, McGrath P, Strodel W, and Freeman JW. Differential expression of transforming growth factor beta receptors in human pancreatic adeno-carcinoma. Anticancer Res 20: 43-51, 2000.
47. Whitnall M, Howard J, Ponka P, and Richardson DR. A class of iron chelators with a wide spectrum of potent antitumor activity that overcomes resistance to chemotherapeutics. Proc Natl Acad Sci USA 103: 14901-14906, 2006.
48. Yang G and Yang X. Smad4-mediated TGF-beta signaling in tumorigenesis. Int J Biol Sci 6: 1-8, 2010.
49. Yang Y, Zhou F, Fang Z, Wang L, Li Z, Sun L, Wang C, Yao W, Cai X, Jin J, and Zha X. Post-transcriptional and post-translational regulation of PTEN by transforming growth factor-beta1. J Cell Biochem 106: 1102-1112, 2009.
50. Yu Y, Kovacevic Z, and Richardson DR. Tuning cell cycle regulation with an iron key. Cell Cycle 6: 1982-1994, 2007.