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01-11-2007 | Research Paper

Understanding h-prune biology in the fight against cancer

Authors: Natascia Marino, Massimo Zollo

Published in: Clinical & Experimental Metastasis | Issue 8/2007

Abstract

The h-prune protein is a member of the DHH protein superfamily, and its overexpression in breast, colorectal and gastric cancers correlates with depth of invasion and degree of lymph-node metastasis. Taken together with the observation that h-prune is highly expressed in metastatic breast cancer, this suggests that h-prune can be used as a marker for the identification of subsets of cancer patients with highly aggressive tumours. H-prune possesses a phosphodiesterase (cAMP-PDE) activity, and inhibition of PDE activity with dipyridamole suppresses cell motility. H-prune interacts with nm23-H1, GSK-3β and gelsolin. Although a correlation between an h-prune PDE activity and cellular motility has been shown, GSK-3β does not affect the PDE activity of h-prune. Inhibition of the interactions between h-prune and GSK-3β and nm23-H1 additively suppresses the migration of colon cancer and breast cancer cells, thus suggesting that h-prune regulates cell motility by two different means of action: through its PDE activity and in its interactions with protein partners. Therefore, the identification of highly specific inhibitors of h-prune should be useful in the development of drugs to treat cancer metastasis.

Al-Hajj M (2007) Cancer stem cells and oncology therapeutics. Curr Opin Oncol 19:61–64PubMedCrossRef

Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100:3983–3988PubMedCrossRef

Anisimov VN, Ukraintseva SV, Yashin AI (2005) Cancer in rodents: does it tell us about cancer in humans? Nat Rev Cancer 5:807–819PubMedCrossRef

Aravind L, Koonin EV (1998) A novel family of predicted phosphoesterases includes Drosophila prune protein and bacterial RecJ exonuclease. Trends Biochem Sci 23:17–19PubMedCrossRef

Baba H, Urano T, Okada K, Furukawa K, Nakayama E, Tanaka H, Iwasaki K, Shiku H (1995) Two isotypes of murine nm23/nucleoside diphosphate kinase, nm23-M1 and nm23-M2, are involved in metastatic suppression of a murine melanoma line. Cancer Res 55:1977–1981PubMed

Banfi S, Borsani G, Rossi E, Bernard L, Guffanti A, Rubboli F, Marchitiello A, Giglio S, Coluccia E, Zollo M, Zuffardi O, Ballabio A (1996) Identification and mapping of human cDNAs homologous to Drosophila mutant genes through EST database searching. Nat Genet 13:167–174PubMedCrossRef

Beavo JA, Brunton LL (2002) Cyclic nucleotide research—still expanding after half a century. Nat Rev Mol Cell Biol 3:710–718PubMedCrossRef

Bemis LT, Schedin P (2000) Reproductive state of rat mammary gland stroma modulates human breast cancer cell migration and invasion. Cancer Res 60:3414–3418PubMed

Bissell MJ, Labarge MA (2005) Context, tissue plasticity, and cancer: are tumor stem cells also regulated by the microenvironment? Cancer Cell 7:17–23PubMed

10.

Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, Nieto MA (2002) Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene 21:3241–3246PubMedCrossRef

11.

Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3:730–737PubMedCrossRef

12.

Brabletz T, Jung A, Spaderna S, Hlubek F, Kirchner T (2005) Opinion: migrating cancer stem cells—an integrated concept of malignant tumour progression. Nat Rev Cancer 5:744–749PubMedCrossRef

13.

Card GL, Blasdel L, England BP, Zhang C, Suzuki Y, Gillette S, Fong D, Ibrahim PN, Artis DR, Bollag G, Milburn MV, Kim SH, Schlessinger J, Zhang KY (2005) A family of phosphodiesterase inhibitors discovered by cocrystallography and scaffold-based drug design. Nat Biotechnol 23:201–207PubMedCrossRef

14.

D′Angelo A, Garzia L, Andre A, Carotenuto P, Aglio V, Guardiola O, Arrigoni G, Cossu A, Palmieri G, Aravind L, Zollo M (2004) Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis. Cancer Cell 5:137–149PubMedCrossRef

15.

Dean M, Fojo T, Bates S (2005) Tumour stem cells and drug resistance. Nat Rev Cancer 5:275–284PubMedCrossRef

16.

Di Cristofano A, De Acetis M, Koff A, Cordon-Cardo C, Pandolfi PP (2001) Pten and p27KIP1 cooperate in prostate cancer tumor suppression in the mouse. Nat Genet 27:222–224PubMedCrossRef

17.

Dosaka-Akita H, Hommura F, Fujita H, Kinoshita I, Nishi M, Morikawa T, Katoh H, Kawakami Y, Kuzumaki N (1998) Frequent loss of gelsolin expression in non-small cell lung cancers of heavy smokers. Cancer Res 58:322–327PubMed

18.

Essayan DM (2001) Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol 108:671–680PubMedCrossRef

19.

Florenes VA, Aamdal S, Myklebost O, Maelandsmo GM, Bruland OS, Fodstad O (1992) Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. Cancer Res 52:6088–6091PubMed

20.

Forus A, D′Angelo A, Henriksen J, Merla G, Maelandsmo GM, Florenes VA, Olivieri S, Bjerkehagen B, Meza-Zepeda LA, del Vecchio Blanco F, Muller C, Sanvito F, Kononen J, Nesland JM, Fodstad O, Reymond A, Kallioniemi OP, Arrigoni G, Ballabio A, Myklebost O, Zollo M (2001) Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas-a possible mechanism for altering the nm23-H1 activity. Oncogene 20:6881–6890PubMedCrossRef

21.

Fujita N, Jaye DL, Kajita M, Geigerman C, Moreno CS, Wade PA (2003) MTA3, a Mi-2/NuRD complex subunit, regulates an invasive growth pathway in breast cancer. Cell 113:207–219PubMedCrossRef

22.

Garzia L, D′Angelo A, Amoresano A, Knauer SK, Cirulli C, Campanella C, Stauber RH, Steegborn C, Iolascon A, Zollo M (2007) Phosphorylation of nm23H1 by CKI induces complex formation with h-prune and promotes cell motility. Oncogene. doi:10.1038/sj.onc.1210822 PubMed

23.

Garzia L, Roma C, Tata N, Pagnozzi D, Pucci P, Zollo M (2006) H-prune–nm23-H1 protein complex and correlation to pathways in cancer metastasis. J Bioenerg Biomembr 38:205–213PubMedCrossRef

24.

Groszer M, Erickson R, Scripture-Adams DD, Lesche R, Trumpp A, Zack JA, Kornblum HI, Liu X, Wu H (2001) Negative regulation of neural stem/progenitor cell proliferation by the Pten tumor suppressor gene in vivo. Science 294:2186–2189PubMedCrossRef

25.

Hannigan G, Troussard AA, Dedhar S (2005) Integrin-linked kinase: a cancer therapeutic target unique among its ILK. Nat Rev Cancer 5:51–63PubMedCrossRef

26.

Hartsough MT, Steeg PS (2000) Nm23/nucleoside diphosphate kinase in human cancers. J Bioenerg Biomembr 32:301–308PubMedCrossRef

27.

Hejna M, Raderer M, Zielinski CC (1999) Inhibition of metastases by anticoagulants. J Natl Cancer Inst 91:22–36PubMedCrossRef

28.

Henrique D, Hirsinger E, Adam J, Le Roux I, Pourquie O, Ish-Horowicz D, Lewis J (1997) Maintenance of neuroepithelial progenitor cells by Delta-Notch signalling in the embryonic chick retina. Curr Biol 7:661–670PubMedCrossRef

29.

Honn KV, Tang DG, Crissman JD (1992) Platelets and cancer metastasis: a causal relationship? Cancer Metastasis Rev 11:325–351PubMedCrossRef

30.

Kang Y, Massague J (2004) Epithelial-mesenchymal transitions: twist in development and metastasis. Cell 118:277–279PubMedCrossRef

31.

Kantor JD, McCormick B, Steeg PS, Zetter BR (1993) Inhibition of cell motility after nm23 transfection of human and murine tumor cells. Cancer Res 53:1971–1973PubMed

32.

Kobayashi T, Hino S, Oue N, Asahara T, Zollo M, Yasui W, Kikuchi A (2006) Glycogen synthase kinase 3 and h-prune regulate cell migration by modulating focal adhesions. Mol Cell Biol 26:898–911PubMedCrossRef

33.

Lacombe ML, Milon L, Munier A, Mehus JG, Lambeth DO (2000) The human Nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr 32:247–258PubMedCrossRef

34.

Lee HK, Driscoll D, Asch H, Asch B, Zhang PJ (1999) Downregulated gelsolin expression in hyperplastic and neoplastic lesions of the prostate. Prostate 40:14–19PubMedCrossRef

35.

Leone A, Flatow U, King CR, Sandeen MA, Margulies IM, Liotta LA, Steeg PS (1991) Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell 65:25–35PubMedCrossRef

36.

Leone A, Flatow U, VanHoutte K, Steeg PS (1993) Transfection of human nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potential, colonization and enzymatic activity. Oncogene 8:2325–2333PubMed

37.

Lessard J, Sauvageau G (2003) Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature 423:255–260PubMedCrossRef

38.

McLean GW, Carragher NO, Avizienyte E, Evans J, Brunton VG, Frame MC (2005) The role of focal-adhesion kinase in cancer—a new therapeutic opportunity. Nat Rev Cancer 5:505–515PubMedCrossRef

39.

Middelhaufe S, Garzia L, Ohndorf UM, Kachholz B, Zollo M, Steegborn C (2007) Domain mapping on the human metastasis regulator protein h-Prune reveals a C-terminal dimerization domain. Biochem J 407:199–205PubMedCrossRef

40.

Nierodzik ML, Karpatkin S (2006) Thrombin induces tumor growth, metastasis, and angiogenesis: evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell 10:355–362PubMedCrossRef

41.

Niitsu N, Okabe-Kado J, Okamoto M, Takagi T, Yoshida T, Aoki S, Hirano M, Honma Y (2001) Serum nm23-H1 protein as a prognostic factor in aggressive non-Hodgkin lymphoma. Blood 97:1202–1210PubMedCrossRef

42.

Oue N, Yoshida K, Noguchi T, Sentani K, Kikuchi A, Yasui W (2007) Increased expression of h-prune is associated with tumor progression and poor survival in gastric cancer. Cancer Sci 98:1198–1205PubMedCrossRef

43.

Palmieri D, Halverson DO, Ouatas T, Horak CE, Salerno M, Johnson J, Figg WD, Hollingshead M, Hursting S, Berrigan D, Steinberg SM, Merino MJ, Steeg PS (2005) Medroxyprogesterone acetate elevation of Nm23-H1 metastasis suppressor expression in hormone receptor-negative breast cancer. J Natl Cancer Inst 97:632–642PubMedCrossRef

44.

Pardal R, Clarke MF, Morrison SJ (2003) Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 3:895–902PubMedCrossRef

45.

Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423:302–305PubMedCrossRef

46.

Polakis P (1999) The oncogenic activation of beta-catenin. Curr Opin Genet Dev 9:15–21PubMedCrossRef

47.

Pritsker M, Ford NR, Jenq HT, Lemischka IR (2006) Genomewide gain-of-function genetic screen identifies functionally active genes in mouse embryonic stem cells. Proc Natl Acad Sci USA 103:6946–6951PubMedCrossRef

48.

Rangarajan A, Weinberg RA (2003) Opinion: comparative biology of mouse versus human cells: modelling human cancer in mice. Nat Rev Cancer 3:952–959PubMedCrossRef

49.

Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL (2003) A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature 423:409–414PubMedCrossRef

50.

Reymond A, Volorio S, Merla G, Al-Maghtheh M, Zuffardi O, Bulfone A, Ballabio A, Zollo M (1999) Evidence for interaction between human PRUNE and nm23-H1 NDPKinase. Oncogene 18:7244–7252PubMedCrossRef

51.

Russell RL, Geisinger KR, Mehta RR, White WL, Shelton B, Kute TE (1997) nm23—relationship to the metastatic potential of breast carcinoma cell lines, primary human xenografts, and lymph node negative breast carcinoma patients. Cancer 79:1158–1165PubMedCrossRef

52.

Singh SK, Clarke ID, Terasaki M, Bonn VE, Hawkins C, Squire J, Dirks PB (2003) Identification of a cancer stem cell in human brain tumors. Cancer Res 63:5821–5828PubMed

53.

Smith PG, Thomas HD, Barlow HC, Griffin RJ, Golding BT, Calvert AH, Newell DR, Curtin NJ (2001) In vitro and in vivo properties of novel nucleoside transport inhibitors with improved pharmacological properties that potentiate antifolate activity. Clin Cancer Res 7:2105–2113PubMed

54.

Steeg PS, Bevilacqua G, Kopper L, Thorgeirsson UP, Talmadge JE, Liotta LA, Sobel ME (1988) Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 80:200–204PubMedCrossRef

55.

Suzuki E, Ota T, Tsukuda K, Okita A, Matsuoka K, Murakami M, Doihara H, Shimizu N (2004) nm23-H1 reduces in vitro cell migration and the liver metastatic potential of colon cancer cells by regulating myosin light chain phosphorylation. Int J Cancer 108:207–211PubMedCrossRef

56.

Thiery JP (2003) Epithelial-mesenchymal transitions in development and pathologies. Curr Opin Cell Biol 15:740–746PubMedCrossRef

57.

Thor AD, Edgerton SM, Liu S, Moore DH 2nd, Kwiatkowski DJ (2001) Gelsolin as a negative prognostic factor and effector of motility in erbB-2-positive epidermal growth factor receptor-positive breast cancers. Clin Cancer Res 7:2415–2424PubMed

58.

Timmons L, Shearn A (1996) Germline transformation using a prune cDNA rescues prune/killer of prune lethality and the prune eye color phenotype in Drosophila. Genetics 144:1589–1600PubMed

59.

Wechsler-Reya R, Scott MP (2001) The developmental biology of brain tumors. Annu Rev Neurosci 24:385–428PubMedCrossRef

60.

Wechsler-Reya RJ, Scott MP (1999) Control of neuronal precursor proliferation in the cerebellum by Sonic Hedgehog. Neuron 22:103–114PubMedCrossRef

61.

Wetmore C (2003) Sonic hedgehog in normal and neoplastic proliferation: insight gained from human tumors and animal models. Curr Opin Genet Dev 13:34–42PubMedCrossRef

62.

Xue C, Plieth D, Venkov C, Xu C, Neilson EG (2003) The gatekeeper effect of epithelial-mesenchymal transition regulates the frequency of breast cancer metastasis. Cancer Res 63:3386–3394PubMed

63.

Zollo M, Andre A, Cossu A, Sini MC, D′Angelo A, Marino N, Budroni M, Tanda F, Arrigoni G, Palmieri G (2005) Overexpression of h-prune in breast cancer is correlated with advanced disease status. Clin Cancer Res 11:199–205PubMed

Title: Understanding h-prune biology in the fight against cancer
Authors: Natascia Marino
Massimo Zollo
Publication date: 01-11-2007
Publisher: Springer Netherlands
Published in: Clinical & Experimental Metastasis / Issue 8/2007
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-007-9109-3

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