Taiwanese Journal of Obstetrics and Gynecology
Volume 45, Issue 2 , Pages 107-113 , June 2006

NM23-H1: a Metastasis-Associated Gene

  • Yi-Torng Tee

      Affiliations

    • Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan
    • Institute of Medicine, Taichung, Taiwan
    • ,
  • Gin-Den Chen

      Affiliations

    • Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan
    • School of Medicine, Taichung, Taiwan
    • ,
  • Long-Yau Lin

      Affiliations

    • Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan
    • Institute of Medicine, Taichung, Taiwan
    • School of Medicine, Taichung, Taiwan
    • ,
  • Jiunn-Liang Ko

      Affiliations

    • Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung, Taiwan
    • ,
  • Po-Hui Wang

      Affiliations

    • Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, Taichung, Taiwan
    • Institute of Medicine, Taichung, Taiwan
    • School of Medicine, Taichung, Taiwan
    • Corresponding Author InformationCorrespondence to: Dr Po-Hui Wang, Department of Obstetrics and Gynecology, Chung Shan Medical University Hospital, 110, Section 1, Chien-Kuo North Road, Taichung 40201, Taiwan

,Accepted 21 March 2006.

References 

  1. Hanahan D , Weinberg RA . The hallmarks of cancer . Cell . 2000;100:57–70
  2. Steeg PS . Metastasis suppressors alter the signal transduction of cancer cells . Nat Rev Cancer . 2003;3:55–63
  3. Fidler IJ . Critical determinants of metastasis . Semin Cancer Biol . 2002;12:89–96
  4. Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, et al. Evidence for a novel gene associated with low tumor metastatic potential . J Natl Cancer Inst . 1988;80:200–204
  5. Berg P , Joklik WK . Transphosphorylation between nucleo-side polyphosphates . Nature . 1953;172:1008–1009
  6. Krebs HA , Hems R . Some reactions of adenosine and inosine phosphates in animal tissues . Biochem Biophys Acta . 1953;12:172–180
  7. Cheng YC , Agarwal RP , Parks RE . Erythrocytic nucleoside diphosphokinase. IV. Evidence for electrophoretic heterogeneity . Biochemistry . 1971;10:2139–2143
  8. Cheng YC , Robison B , Parks RE . Demonstration of the heterogeneity of nucleoside diphosphokinase in rat tissues . Biochemistry . 1973;12:5–10
  9. Munoz-Dorado J , Inouye M , Inouye S . Nucleoside diphosphate kinase from Myxococcus xanthus. I. Cloning and sequencing of the gene . J Biol Chem . 1990;265:2702–2706
  10. Lacombe ML , Wallet V , Troll H , Veron M . Functional cloning of a nucleoside diphosphate kinase from Dictyostelium discoideum . J Biol Chem . 1990;265:10012–10018
  11. Kimura N , Shimada N , Nomura K , Watanabe K . Isolation and characterization of a cDNA clone encoding rat nucleoside diphosphate kinase . J Biol Chem . 1990;265:15744–15749
  12. Wallet V, Mutzel R, Troll H, Barzu O, Wurster B, Veron M, et al. Dictyostelium nucleoside diphosphate kinase highly homologous to Nm23 and Awd proteins involved in mammalian tumor metastasis and Drosophila development . J Natl Cancer Inst . 1990;82:1199–1202
  13. Urano T , Takamiya K , Furukawa K , Shiku H . Molecular cloning and functional expression of the second mouse nm23/NDP kinase gene, nm23-M2 . FEBS Lett . 1992;309:358–362
  14. Rosengard AM , Krutzsch HC , Shearn A , et al.   Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development . Nature . 1989;342:177–180
  15. Lacombe ML , Milon L , Munier A , Mehus JG , Lambeth DO . The human Nm23/nucleoside diphosphate kinases . J Bioenerg Biomembr . 2000;32:247–258
  16. Stahl JA , Leone A , Rosengard AM , Porter L , King CR , Steeg PS . Identification of a second human nm23 gene, nm23-H2 . Cancer Res . 1991;51:445–449
  17. Gilles AM , Presecan E , Vonica A , Lascu I . Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of hexameric enzyme . J Biol Chem . 1991;266:8784–8789
  18. Venturelli D , Martinez R , Melotti P , et al.   Overexpression of DR-nm23, a protein encoded by a member of the nm23 gene family, inhibits granulocyte differentiation and induces apoptosis in 32Dc13 myeloid cells . Proc Natl Acad Sci USA . 1995;92:7435–7439
  19. Milon L, Rousseau-Merck MF, Munier A, Erent M, Lascu I, Capeau J, et al. Nm23-H4, a new member of the family of human nm23/nucleoside diphosphate kinase genes localized on chromosome 16p13 . Hum Genet . 1997;99:550–557
  20. Lombardi D , Lacombe ML , Paggi MG . Nm23: unraveling its biological function in cell differentiation . J Cell Physiol . 2000;182:144–149
  21. Munier A , Feral C , Milon L , et al.   A new human Nm23 homologue (Nm23-H5) specifically expressed in testis germinal cells . FEBS Lett . 1998;434:289–294
  22. Mehus JG , Deloukas P , Lambeth DO . NME6: a new member of the Nm23/nucleoside diphosphate kinase gene family located on human chromosome 3p21.3 . Hum Genet . 1999;104:454–459
  23. Agarwal RP , Robinson B , Parks RE . Nucleoside diphosphokinase from human erythrocyte . Methods Enzymol . 1978;51:376–386
  24. de la Rosa A , Williams RL , Steeg PS . Nm23/nucleoside diphosphate kinase: toward a structural and biochemical understanding of its biological functions . Bioessays . 1995;17:53–62
  25. Garces E , Cleland WW . Kinetic studies of yeast nucleoside diphosphate kinase . Biochemistry . 1969;8:633–640
  26. Leone A, Flatow U, King CR, Sandeen MA, Margulies IM, Liotta LA, et al. Reduced tumor incidence, metastatic potential, and cytokine responsiveness of Nm23-transfected melanoma cells . Cell . 1991;65:25–33
  27. Leone A , Flatow U , VanHoutte K , Steeg PS . Transfection of human Nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potentials, colonization and enzymatic activity . Oncogene . 1993;8:2325–2333
  28. Kantor JD , McCormick B , Steeg PS , Zetter BR . Inhibition of cell motility after Nm23 transfection of human and murine tumor cells . Cancer Res . 1993;53:1971–1973
  29. Palmieri D , Halverson DO , Ouatas T , et al.   Medroxyprogesterone acetate elevation of Nm23-H1 metastasis suppressor expression in hormone receptor-negative breast cancer . J Natl Cancer Inst . 2005;97:632–642
  30. Ouatas T , Halverson D , Steeg PS . Dexamethasone and medroxyprogesterone acetate elevate Nm23-H1 metastasis suppressor gene expression in metastatic human breast carcinoma cells: new uses for old compounds . Clin Cancer Res . 2003;9:3763–3772
  31. Che GW , Zhou QH , Zhu W , et al.   Molecular mechanism of reversing metastatic phenotype in human high-metastatic large cell lung cancer cell line L9981 by nm23-H1 . Ai Zheng . 2005;24:278–284
  32. Che G , Zhou Q , Wang Y , et al.   Effect of Nm23-H1 on reversing malignant phenotype on human lung cancer cell line L9981 . Sheng Wu Yi Xue Gong Cheng Xue Za Zhi . 2005;22:530–534
  33. Lim S , Lee HY , Lee H . Inhibition of colonization and cell-matrix adhesion after Nm23-H1 transfection of human prostate carcinoma cells . Cancer Lett . 1998;133:143–149
  34. MacDonald NJ , Freije JM , Stracke ML , Manrow RE , Steeg PS . Site-directed mutagenesis of Nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells . J Biol Chem . 1996;271:25107–25116
  35. Lee HY , Lee H . Inhibitory activity of Nm23-H1 on invasion and colonization of human prostate carcinoma cells is not mediated by its NDP kinase activity . Cancer Lett . 1999;145:93–99
  36. Freije JM , Blay P , MacDonald NJ , Manrow RE , Steeg PS . Site-directed mutation of Nm23-H1. Mutations lacking motility suppressive capacity upon transfection are deficient in histidine-dependent protein phosphotransferase pathways in vitro . J Biol Chem . 1997;272:5525–5532
  37. Pozzatti R, Muschel R, Williams J, Padmanabhan R, Howard B, Liotta L, et al. Primary rat embryo cells transformed by one or two oncogenes show different metastatic potentials . Science . 1986;232:223–227
  38. Wyllie AH , Rose KA , Morris RG , Steel CM , Foster E , Spandidos DA . Rodent fibroblast tumors expressing human myc and ras genes: growth, metastasis and endogenous oncogene expression . Br J Cancer . 1987;56:251–259
  39. Giehl K . Oncogenic Ras in tumour progression and metastasis . Biol Chem . 2005;386:193–205
  40. Morrison D . KSR: a MAPK scaffold of the ras pathway? . J Cell Sci . 2001;114:1609–1612
  41. Roy F , Laberge G , Douziech M , Ferland-McCollough D , Therrien M . SKR is a scaffold required for activation of the ERK/MAPK module . Genes Dev . 2002;16:427–438
  42. Salerno M , Palmieri D , Bouadis A , Halverson D , Steeg PS . Nm23-H1 metastasis suppressor expression level influences the binding properties, stability, and function of the kinase suppressor of Ras (SKR1) Erk scaffold in breast carcinoma cells . Mol Cell Biol . 2005;25:1379–1388
  43. Cacace AM, Michaud NR, Therrien M, Mathes K, Copeland T, Rubin GM, et al. Identification of constitutive and ras-inducible phosphylation sites of KSR; implications for 14–3-3 binding, mitogen activated protein kinase binding and KSR overexpression . Mol Cell Bol . 1999;19:229–240
  44. Volle D, Fulton JA, Chaika OV, McDermott K, Huang H, Steinke LA, et al. Phosphorylation of the kinase suppressor of ras by associated kinases . Biochemistry . 1999;38:5130–5137
  45. Hartsough MT , Morrison DK , Salerno M , et al.   Nm23-H1 metastasis suppressor phosphorylation of kinase suppressor of Ras via a histidine protein kinase pathway . J Biol Chem . 2002;277:32389–32399
  46. Valentijn LJ , Koppen A , van Asperen R , Root HA , Haneveld F , Versteeg R . Inhibition of a new differentiation pathway in neuroblastoma by copy number defects of N-myc, Cdc42, and nm23 genes . Cancer Res . 2005;65:3136–3145
  47. Otero AS . NM23/nucleoside diphosphate kinase and signal transduction . J Bioenerg Biomembr . 2000;32:269–275
  48. Biggs J , Hersperger E , Steeg PS , Liotta LA , Shearn A . A Drosophila gene that is homologous to a mammalian gene associated with tumor metastasis codes for a nucleoside diphosphate kinase . Cell . 1990;63:933–940
  49. Otero AS . Copurification of vimentin, energy metabolism enzymes, and a MER5 homolog with nucleoside diphosphate kinase. Identification of tissue-specific interactions . J Biol Chem . 1997;272:14690–14694
  50. Pinon VP , Millot G , Munier A , et al.   Cytoskeletal association of the A and B nucleoside diphosphate kinases of interphasic but not mitotic human carcinoma cell lines: specific nuclear localization of the B subunit . Exp Cell Res . 1999;246:355–367
  51. Eckes B , Dogic D , Colucci-Guyon E , et al.   Impaired mechanical stability, migration and contractile capacity in vimentin-deficient fibroblasts . J Cell Sci . 1998;111:1897–1907
  52. Gilles C, Polette M, Zahm JM, Tournier JM, Volders L, Foidart JM, et al. Vimentin contributes to human mammary epithelial cell migration . J Cell Sci . 1999;112:4615–4625
  53. Ouatas T , Salerno M , Palmieri D , Steeg PS . Basic and translational advances in cancer metastasis: Nm23 . J Bioenerg Biomembr . 2003;35:73–79
  54. Sirotkovic-Skerlev M , Krizanac S , Kapitanovic S , Husnjak K , Unusic J , Pavelic K . Expression of c-myc, erb-2, erbB-2, p53 and nm23-H1 gene product in benign and malignant breast lesions: coexpression and correlation with clinicopathologic parameters . Exp Mol Pathol . 2005;79:42–50
  55. Muller W , Schneiders A , Hommel G , Gabbert HE . Expression of Nm23 in gastric carcinoma: association with tumor progression and poor prognosis . Cancer . 1998;83:2481–2487
  56. Lee CS , Pirdas A , Lee MW . Immunohistochemical demonstration of the Nm23-H1 gene product in human malignant melanoma and Spitz nevi . Pathology . 1996;28:220–224
  57. Kapitanovic S , Cacev T , Berkovic M , et al.   Nm23-H1 expression and loss of heterozygosity in colon adenocarcinoma . J Clin Pathol . 2004;57:1312–1318
  58. Zou M , Shi Y , Al-Sedairy S , Farid NR . High levels of Nm23 gene expression in advanced stage of thyroid carcinomas . Br J Cancer . 1993;68:385–388
  59. Ferenc T , Lewinski A , Lange D , et al.   Analysis of Nm23-H1 protein immunoreactivity in follicular thyroid tumors . Pol J Pathol . 2004;55:149–153
  60. Leone A , Seeger RC , Hong CM , et al.   Evidence for Nm23 RNA overexpression, DNA amplification and mutation in aggressive childhood neuroblastomas . Oncogene . 1993;8:855–865
  61. Oda Y , Naka T , Takeshita M , Iwamoto Y , Tsuneyoshi M . Comparison of histological changes and changes in Nm23 and c-MET expression between primary and metastatic sites in osteosarcoma: a clinicopathologic and immunohisto-chemical study . Hum Pathol . 2000;31:709–716
  62. Szumilo J , Skomra D , Chibowski D , Dabrowski A , Wallner G , Maciejewski R . Immunoexpression of Nm23 in advanced esophageal squamous cell carcinoma . Folia Histochem Cytobiol . 2002;40:377–380
  63. Mandai M , Konishi I , Koshiyama M , et al.   Expression of metastasis-related Nm23-H1 and Nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EFR, c-erbB-2, and c-erB-3 genes, and sex steroid receptor expression . Cancer Res . 1994;54:1825–1830
  64. Tas F, Tuzlali S, Aydiner A, Saip P, Salihoglu Y, Iplikci A, et al. Prognostic role of Nm23 gene expression in patients with ovarian cancer . Am J Clin Oncol . 2002;25:164–167
  65. Tomic S , Ilic Forko J , Babic D , Sundov D , Kuret S , Andelinovic S . c-erbB-2, p53, and Nm23 proteins as prognostic factors in patients with epithelial ovarian carcinoma . Croat Med J . 2003;44:429–434
  66. Marone M , Scambia G , Ferrandina G , et al.   Nm23 expression in endometrial and cervical cancer: inverse correlation with lymph node involvement and myometrial invasion . Br J Cancer . 1996;74:1063–1068
  67. Mandai M , Konishi I , Koshiyama M , et al.   Altered expression of Nm23 H1 and c-erbB-2 proteins have prognostic significance in adenocarcinoma but not in squamous cell carcinoma of the uterine cervix . Cancer . 1995;75:2523–2529
  68. Kristensen GB , Holm R , Abeler VM , Trope CG . Evaluation of the prognostic significance of Nm23/NDP kinase protein expression in cervical carcinoma: an immunohisto-chemical study . Gynecol Oncol . 1996;61:378–383
  69. Wang PH , Ko JL , Chang H , Lin LY . Clinical significance of high Nm23-H1 expression in intraepithelial neoplasia and early-stage squamous cell carcinoma of the uterine cervix . Gynecol Obstet Invest . 2003;55:14–19
  70. Sarac E, Ayhan A, Ertoy D, Tuncer ZS, Yasui W, Tahara E, et al. Nm23 expression in carcinoma of the uterine cervix . Eur J Gynaecol Oncol . 1998;19:312–315
  71. Chen HY , Hsu CT , Lin WC , Tsai HD , Chang WC . Prognostic value of Nm23 expression in Stage IB1 cervical carcinoma . Jpn J Clin Oncol . 2001;31:327–332
  72. Wang PH , Chang H , Ko JL , Lin LY . Nm23-H1 immunohisto-chemical expression in multisteps of cervical carcinogenesis . Int J Gynecol Cancer . 2003;13:325–330
  73. Ravazoula P , Aletra C , Kourounis G , Ladopoulos I , Tzigounis V . Immunohistochemical analysis of Nm23-H1 expression in human cervical lesions . Eur J Gynaecol Oncol . 2000;21:510–512
  74. Weber G , Jackson RC , Williams JC , Goulding FJ , Eberts TJ . Enzymatic markers of neoplastic transformation and regulation of purine and pyrimidine metabolism . Adv Enzyme Regul . 1977;15:53–77
  75. Ohneda K , Fukuda M , Shimada N , et al.   Increased expression of nucleoside diphosphate kinases/Nm23 in human diploid fibroblasts transformed by SV40 large T antigen or 60Co irradiation . FEBS Lett . 1994;348:273–277

PII: S1028-4559(09)60206-0

doi: 10.1016/S1028-4559(09)60206-0

Taiwanese Journal of Obstetrics and Gynecology
Volume 45, Issue 2 , Pages 107-113 , June 2006

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