Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 384, Issue 4–5, pp 363–372

NME genes in epithelial morphogenesis

REVIEW

Abstract

The NME family of genes encodes highly conserved multifunctional proteins that have been shown to participate in nucleic acid metabolism, energy homeostasis, cell signaling, and cancer progression. Some family members, particularly isoforms 1 and 2, have attracted extensive interests because of their potential anti-metastasis activity. Unfortunately, there have been few consensus mechanistic explanations for this critical function because of the numerous molecular functions ascribed to these proteins, including nucleoside diphosphate kinase, protein kinase, nuclease, transcription factor, growth factor, among others. In addition, different studies showed contradictory prognostic correlations between NME expression levels and tumor progression in clinical samples. Thus, analyses using pliable in vivo systems have become critical for unraveling at least some aspects of the complex functions of this family of genes. Recent works using the Drosophila genetic system have suggested a role for NME in regulating epithelial cell motility and morphogenesis, which has also been demonstrated in mammalian epithelial cell culture. This function is mediated by promoting internalization of growth factor receptors in motile epithelial cells, and the adherens junction components such as E-cadherin and β-catenin in epithelia that form the tissue linings. Interestingly, NME genes in epithelial cells appear to function in a defined range of expression levels. Either down-regulation or over-expression can perturb epithelial integrity, resulting in different aspects of epithelial abnormality. Such biphasic functions provide a plausible explanation for the documented anti-metastatic activity and the suspected oncogenic function. This review summarizes these recent findings and discusses their implications.

Keywords

NME genes Awd Drosophila Epithelial morphogenesis Follicle cell Trachea 

References

  1. Adryan B, Decker HJ, Papas TS, Hsu T (2000) Tracheal development and the von Hippel–Lindau tumor suppressor homolog in Drosophila. Oncogene 19:2803–2811PubMedCrossRefGoogle Scholar
  2. Affolter M, Bellusci S, Itoh N, Shilo B, Thiery JP, Werb Z (2003) Tube or not tube: remodeling epithelial tissues by branching morphogenesis. Dev Cell 4:11–18PubMedCrossRefGoogle Scholar
  3. An HJ, Kim DS, Park YK, Kim SK, Choi YP, Kang S, Ding B, Cho NH (2006) Comparative proteomics of ovarian epithelial tumors. J Proteome Res 5:1082–1090PubMedCrossRefGoogle Scholar
  4. Anwar S, Frayling IM, Scott NA, Carlson GL (2004) Systematic review of genetic influences on the prognosis of colorectal cancer. Br J Surg 91:1275–1291PubMedCrossRefGoogle Scholar
  5. Ayhan A, Usubutun A, Ozen H, Yasui W, Tahara E (1998) nm23 protein expression in renal cell tumors: the role of the cell type. Oncol Rep 5:979–983PubMedGoogle Scholar
  6. Bailly E, McCaffrey M, Touchot N, Zahraoui A, Goud B, Bornens M (1991) Phosphorylation of two small GTP-binding proteins of the Rab family by p34cdc2. Nature 350:715–718PubMedCrossRefGoogle Scholar
  7. Berg P, Joklik WK (1953) Transphosphorylation between nucleoside polyphosphates. Nature 172:1008–1009PubMedCrossRefGoogle Scholar
  8. Besant PG, Tan E, Attwood PV (2003) Mammalian protein histidine kinases. Int J Biochem Cell Biol 35:297–309PubMedCrossRefGoogle Scholar
  9. Betschinger J, Eisenhaber F, Knoblich JA (2005) Phosphorylation-induced autoinhibition regulates the cytoskeletal protein Lethal (2) giant larvae. Curr Biol 15:276–282PubMedCrossRefGoogle Scholar
  10. Bianco A, Poukkula M, Cliffe A, Mathieu J, Luque CM, Fulga TA, Rorth P (2007) Two distinct modes of guidance signalling during collective migration of border cells. Nature 448:362–365PubMedCrossRefGoogle Scholar
  11. Biggs J, Tripoulas N, Hersperger E, Dearolf C, Shearn A (1988) Analysis of the lethal interaction between the prune and Killer of prune mutations of Drosophila. Genes Dev 2:1333–1343PubMedCrossRefGoogle Scholar
  12. Biggs J, Hersperger E, Steeg PS, Liotta LA, Shearn A (1990) A Drosophila gene that is homologous to a mammalian gene associated with tumor metastasis codes for a nucleoside diphosphate kinase. Cell 63:933–940PubMedCrossRefGoogle Scholar
  13. Bilder D, Li M, Perrimon N (2000) Cooperative regulation of cell polarity and growth by Drosophila tumor suppressors. Science 289:113–116PubMedCrossRefGoogle Scholar
  14. Bilder D, Schober M, Perrimon N (2003) Integrated activity of PDZ protein complexes regulates epithelial polarity. Nat Cell Biol 5:53–58PubMedCrossRefGoogle Scholar
  15. Boissan M, Wendum D, Arnaud-Dabernat S, Munier A, Debray M, Lascu I, Daniel JY, Lacombe ML (2005) Increased lung metastasis in transgenic NM23-Null/SV40 mice with hepatocellular carcinoma. J Natl Cancer Inst 97:836–845PubMedCrossRefGoogle Scholar
  16. Boissan M, De Wever O, Lizarraga F, Wendum D, Poincloux R, Chignard N, Desbois-Mouthon C, Dufour S, Nawrocki-Raby B, Birembaut P, Bracke M, Chavrier P, Gespach C, Lacombe ML (2010) Implication of metastasis suppressor NM23-H1 in maintaining adherens junctions and limiting the invasive potential of human cancer cells. Cancer Res 70:7710–7722PubMedCrossRefGoogle Scholar
  17. Cormont M, Tanti JF, Zahraoui A, Van Obberghen E, Le Marchand-Brustel Y (1994) Rab4 is phosphorylated by the insulin-activated extracellular-signal-regulated kinase ERK1. Eur J Biochem 219:1081–1085PubMedCrossRefGoogle Scholar
  18. Cuello F, Schulze RA, Heemeyer F, Meyer HE, Lutz S, Jakobs KH, Niroomand F, Wieland T (2003) Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Complex formation of NDPK B with Gbeta gamma dimers and phosphorylation of His-266 IN Gbeta. J Biol Chem 278:7220–7226PubMedCrossRefGoogle Scholar
  19. Dammai V, Adryan B, Lavenburg KR, Hsu T (2003) Drosophila awd, the homolog of human nm23, regulates FGF receptor levels and functions synergistically with shi/dynamin during tracheal development. Genes Dev 17:2812–2824PubMedCrossRefGoogle Scholar
  20. Dearolf CR, Hersperger E, Shearn A (1988a) Developmental consequences of awdb3, a cell-autonomous lethal mutation of Drosophila induced by hybrid dysgenesis. Dev Biochem 129:159–168Google Scholar
  21. Dearolf CR, Tripoulas N, Biggs J, Shearn A (1988b) Molecular consequences of awdb3, a cell-autonomous lethal mutation of Drosophila induced by hybrid dysgenesis. Dev Biol 129:169–178PubMedCrossRefGoogle Scholar
  22. Desvignes T, Pontarotti P, Fauvel C, Bobe J (2009) Nme protein family evolutionary history, a vertebrate perspective. BMC Evol Biol 9:256PubMedCrossRefGoogle Scholar
  23. Dobens LL, Raftery LA (2000) Integration of epithelial patterning and morphogenesis in Drosophila ovarian follicle cells. Dev Dyn 218:80–93PubMedCrossRefGoogle Scholar
  24. Duchek P, Somogyi K, Jekely G, Beccari S, Rorth P (2001) Guidance of cell migration by the Drosophila PDGF/VEGF receptor. Cell 107:17–26PubMedCrossRefGoogle Scholar
  25. Engel M, Veron M, Theisinger B, Lacombe ML, Seib T, Dooley S, Welter C (1995) A novel serine/threonine-specific protein phosphotransferase activity of Nm23/nucleoside-diphosphate kinase. Eur J Biochem 234:200–207PubMedCrossRefGoogle Scholar
  26. Fan CL, Hall LM, Skrinska AJ, Brown GM (1976) Correlation of guanosine triphosphate cyclohydrolase activity and the synthesis of pterins in Drosophila melanogaster. Biochem Genet 14:271–280PubMedCrossRefGoogle Scholar
  27. Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J (2003) Tumor suppressor NM23-H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the nucleosome assembly protein SET is its inhibitor. Cell 112:659–672PubMedCrossRefGoogle Scholar
  28. Freije JM, Blay P, MacDonald NJ, Manrow RE, Steeg PS (1997) 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 272:5525–5532PubMedCrossRefGoogle Scholar
  29. Galani E, Sgouros J, Petropoulou C, Janinis J, Aravantinos G, Dionysiou-Asteriou D, Skarlos D, Gonos E (2002) Correlation of MDR-1, nm23-H1 and H Sema E gene expression with histopathological findings and clinical outcome in ovarian and breast cancer patients. Anticancer Res 22:2275–2280PubMedGoogle Scholar
  30. Ghabrial A, Luschnig S, Metzstein MM, Krasnow MA (2003) Branching morphogenesis of the Drosophila tracheal system. Annu Rev Cell Dev Biol 19:623–647PubMedCrossRefGoogle Scholar
  31. Glazer L, Shilo BZ (1991) The Drosophila FGF-R homolog is expressed in the embryonic tracheal system and appears to be required for directed tracheal cell extension. Genes Dev 5:697–705PubMedCrossRefGoogle Scholar
  32. Harlozinska A, Bar JK, Gerber J (1996) nm23 expression in tissue sections and tumor effusion cells of ovarian neoplasms. Int J Cancer 69:415–419PubMedCrossRefGoogle Scholar
  33. Harris TJ, Peifer M (2007) aPKC controls microtubule organization to balance adherens junction symmetry and planar polarity during development. Dev Cell 12:727–738PubMedCrossRefGoogle Scholar
  34. Heimann R, Hellman S (2000) Individual characterisation of the metastatic capacity of human breast carcinoma. Eur J Cancer 36:1631–1639PubMedCrossRefGoogle Scholar
  35. Hiasa Y, Konishi N, Tao M, Matsuda H, Tsumatani K, Nakamura Y, Kitahori Y, Ozono S, Hirao Y, Okajima E (1996) Different expression of nm23-H1 and nm23-H2 protein with proliferative activities in various sizes of human renal cell carcinoma. Oncology 53:79–87PubMedCrossRefGoogle Scholar
  36. Hikita ST, Kosik KS, Clegg DO, Bamdad C (2008) MUC1* mediates the growth of human pluripotent stem cells. PLoS ONE 3:e3312PubMedCrossRefGoogle Scholar
  37. Hippe HJ, Lutz S, Cuello F, Knorr K, Vogt A, Jakobs KH, Wieland T, Niroomand F (2003) Activation of heterotrimeric G proteins by a high energy phosphate transfer via nucleoside diphosphate kinase (NDPK) B and Gbeta subunits. Specific activation of Gsalpha by an NDPK B.Gbetagamma complex in H10 cells. J Biol Chem 278:7227–7233PubMedCrossRefGoogle Scholar
  38. Hippe HJ, Wolf NM, Abu-Taha I, Mehringer R, Just S, Lutz S, Niroomand F, Postel EH, Katus HA, Rottbauer W, Wieland T (2009) The interaction of nucleoside diphosphate kinase B with Gbetagamma dimers controls heterotrimeric G protein function. Proc Natl Acad Sci USA 106:16269–16274PubMedCrossRefGoogle Scholar
  39. Hiroi T (2009) Regulation of epithelial junctions by proteins of the ADP-ribosylation factor family. Front Biosci 14:717–730PubMedCrossRefGoogle Scholar
  40. Howlett AR, Petersen OW, Steeg PS, Bissell MJ (1994) A novel function for the nm23-H1 gene: overexpression in human breast carcinoma cells leads to the formation of basement membrane and growth arrest. J Natl Cancer Inst 86:1838–1844PubMedCrossRefGoogle Scholar
  41. Hsouna A, Nallamothu G, Kose N, Guinea M, Dammai V, Hsu T (2010) Drosophila von Hippel–Lindau tumor suppressor gene function in epithelial tubule morphogenesis. Mol Cell Biol 30:3779–3794PubMedCrossRefGoogle Scholar
  42. Hsu T, Adereth Y, Kose N, Dammai V (2006) Endocytic function of von Hippel–Lindau tumor suppressor protein regulates surface localization of fibroblast growth factor receptor 1 and cell motility. J Biol Chem 281:12069–12080PubMedCrossRefGoogle Scholar
  43. Humbert PO, Dow LE, Russell SM (2006) The Scribble and Par complexes in polarity and migration: friends or foes? Trends Cell Biol 16:622–630PubMedCrossRefGoogle Scholar
  44. Inoue H, Takahashi M, Oomori A, Sekiguchi M, Yoshioka T (1996) A novel function for nucleoside diphosphate kinase in Drosophila. Biochem Biophys Res Commun 218:887–892PubMedCrossRefGoogle Scholar
  45. Kaelin WG Jr (2002) Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer 2:673–682PubMedCrossRefGoogle Scholar
  46. Kamei T, Matozaki T, Sakisaka T, Kodama A, Yokoyama S, Peng YF, Nakano K, Takaishi K, Takai Y (1999) Coendocytosis of cadherin and c-Met coupled to disruption of cell–cell adhesion in MDCK cells—regulation by Rho, Rac and Rab small G proteins. Oncogene 18:6776–6784PubMedCrossRefGoogle Scholar
  47. Karniguian A, Zahraoui A, Tavitian A (1993) Identification of small GTP-binding rab proteins in human platelets: thrombin-induced phosphorylation of rab3B, rab6, and rab8 proteins. Proc Natl Acad Sci USA 90:7647–7651PubMedCrossRefGoogle Scholar
  48. Klambt C, Glazer L, Shilo BZ (1992) Breathless, a Drosophila FGF receptor homolog, is essential for migration of tracheal and specific midline glial cells. Genes Dev 6:1668–1678PubMedCrossRefGoogle Scholar
  49. Knust E, Bossinger O (2002) Composition and formation of intercellular junctions in epithelial cells. Science 298:1955–1959PubMedCrossRefGoogle Scholar
  50. Krebs HA, Hems R (1953) Some reactions of adenosine and inosine phosphates in animal tissues. Biochim Biophys Acta 12:172–180PubMedCrossRefGoogle Scholar
  51. Krishnan KS, Rikhy R, Rao S, Shivalkar M, Mosko M, Narayanan R, Etter P, Estes PS, Ramaswami M (2001) Nucleoside diphosphate kinase, a source of GTP, is required for dynamin-dependent synaptic vesicle recycling. Neuron 30:197–210PubMedCrossRefGoogle Scholar
  52. Le TL, Yap AS, Stow JL (1999) Recycling of E-cadherin: a potential mechanism for regulating cadherin dynamics. J Cell Biol 146:219–232PubMedGoogle Scholar
  53. Lee T, Hacohen N, Krasnow M, Montell DJ (1996) Regulated Breathless receptor tyrosine kinase activity required to pattern cell migration and branching in the Drosophila tracheal system. Genes Dev 10:2912–2921PubMedCrossRefGoogle Scholar
  54. Ma D, Xing Z, Liu B, Pedigo NG, Zimmer SG, Bai Z, Postel EH, Kaetzel DM (2002) NM23-H1 and NM23-H2 repress transcriptional activities of nuclease-hypersensitive elements in the platelet-derived growth factor-A promoter. J Biol Chem 277:1560–1567PubMedCrossRefGoogle Scholar
  55. MacDonald NJ, Freije JM, Stracke ML, Manrow RE, Steeg PS (1996) 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 271:25107–25116PubMedCrossRefGoogle Scholar
  56. Mandai M, Konishi I, Koshiyama M, Mori T, Arao S, Tashiro H, Okamura H, Nomura H, Hiai H, Fukumoto M (1994) Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression. Cancer Res 54:1825–1830PubMedGoogle Scholar
  57. McDonald JA, Pinheiro EM, Montell DJ (2003) PVF1, a PDGF/VEGF homolog, is sufficient to guide border cells and interacts genetically with Taiman. Development 130:3469–3478PubMedCrossRefGoogle Scholar
  58. Montell DJ (2003) Border-cell migration: the race is on. Nat Rev Mol Cell Biol 4:13–24PubMedCrossRefGoogle Scholar
  59. Nakagawa Y, Tsumatani K, Kurumatani N, Cho M, Kitahori Y, Konishi N, Ozono S, Okajima E, Hirao Y, Hiasa Y (1998) Prognostic value of nm23 protein expression in renal cell carcinomas. Oncology 55:370–376PubMedCrossRefGoogle Scholar
  60. Nallamothu G, Woolworth JA, Dammai V, Hsu T (2008) Awd, the homolog of metastasis suppressor gene Nm23, regulates Drosophila epithelial cell invasion. Mol Cell Biol 28:1964–1973PubMedCrossRefGoogle Scholar
  61. Nallamothu G, Dammai V, Hsu T (2009) Developmental function of Nm23/awd—a mediator of endocytosis. Mol Cell Biochem 329:35–44PubMedCrossRefGoogle Scholar
  62. Nelson WJ (2003) Adaptation of core mechanisms to generate cell polarity. Nature 422:766–774PubMedCrossRefGoogle Scholar
  63. Ohshiro T, Saigo K (1997) Transcriptional regulation of breathless FGF receptor gene by binding of TRACHEALESS/dARNT heterodimers to three central midline elements in Drosophila developing trachea. Development 124:3975–3986PubMedGoogle Scholar
  64. Okabe-Kado J, Kasukabe T, Honma Y, Kobayashi H, Maseki N, Kaneko Y (2009) Extracellular NM23 protein promotes the growth and survival of primary cultured human acute myelogenous leukemia cells. Cancer Sci 100:1885–1894PubMedCrossRefGoogle Scholar
  65. Ouatas T, Salerno M, Palmieri D, Steeg PS (2003) Basic and translational advances in cancer metastasis: Nm23. J Bioenerg Biomembr 35:73–79PubMedCrossRefGoogle Scholar
  66. Ouellet V, Le Page C, Guyot MC, Lussier C, Tonin PN, Provencher DM, Mes-Masson AM (2006) SET complex in serous epithelial ovarian cancer. Int J Cancer 119:2119–2126PubMedCrossRefGoogle Scholar
  67. Pagliarini RA, Xu T (2003) A genetic screen in Drosophila for metastatic behavior. Science 302:1227–1231PubMedCrossRefGoogle Scholar
  68. Palacios F, Price L, Schweitzer J, Collard JG, D’Souza-Schorey C (2001) An essential role for ARF6-regulated membrane traffic in adherens junction turnover and epithelial cell migration. EMBO J 20:4973–4986PubMedCrossRefGoogle Scholar
  69. Palacios F, Schweitzer JK, Boshans RL, D’Souza-Schorey C (2002) ARF6-GTP recruits Nm23-H1 to facilitate dynamin-mediated endocytosis during adherens junctions disassembly. Nat Cell Biol 4:929–936PubMedCrossRefGoogle Scholar
  70. Postel EH, Berberich SJ, Rooney JW, Kaetzel DM (2000) Human NM23/nucleoside diphosphate kinase regulates gene expression through DNA binding to nuclease-hypersensitive transcriptional elements. J Bioenerg Biomembr 32:277–284PubMedCrossRefGoogle Scholar
  71. Ribeiro C, Ebner A, Affolter M (2002) In vivo imaging reveals different cellular functions for FGF and Dpp signaling in tracheal branching morphogenesis. Dev Cell 2:677–683PubMedCrossRefGoogle Scholar
  72. Rørth P (2002) Initiating and guiding migration: lessons from border cells. Trend Cell Biol 12:325–331CrossRefGoogle Scholar
  73. Rosengard AM, Krutzsch HC, Shearn A, Biggs JR, Barker E, Margulies IM, King CR, Liotta LA, Steeg PS (1989) Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development. Nature 342:177–180PubMedCrossRefGoogle Scholar
  74. Sirotkovic-Skerlev M, Krizanac S, Kapitanovic S, Husnjak K, Unusic J, Pavelic K (2005) Expression of c-myc, erbB-2, p53 and nm23-H1 gene product in benign and malignant breast lesions: coexpression and correlation with clinicopathologic parameters. Exp Mol Pathol 79:42–50PubMedCrossRefGoogle Scholar
  75. Srivastava S, Choudhury P, Li Z, Liu G, Nadkarni V, Ko K, Coetzee WA, Skolnik EY (2006) Phosphatidylinositol 3-phosphate indirectly activates KCa3.1 via 14 amino acids in the carboxy terminus of KCa3.1. Mol Biol Cell 17:146–154PubMedCrossRefGoogle Scholar
  76. 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 80:200–204PubMedCrossRefGoogle Scholar
  77. Steeg PS, Palmieri D, Ouatas T, Salerno M (2003) Histidine kinases and histidine phosphorylated proteins in mammalian cell biology, signal transduction and cancer. Cancer Lett 190:1–12PubMedCrossRefGoogle Scholar
  78. Stenmark H (2009) Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 10:513–525PubMedCrossRefGoogle Scholar
  79. Sturtevant AH (1956) A highly specific complementary lethal system in Drosophila melanogaster. Genetics 41:118–123PubMedGoogle Scholar
  80. Sutherland D, Samakovlis C, Krasnow MA (1996) Branchless encodes a Drosophila FGF homolog that controls tracheal cell migration and the pattern of branching. Cell 87:1091–1101PubMedCrossRefGoogle Scholar
  81. Suzuki A, Ohno S (2006) The PAR-aPKC system: lessons in polarity. J Cell Sci 119:979–987PubMedCrossRefGoogle Scholar
  82. Tepass U (2002) Adherens junctions: new insight into assembly, modulation and function. Bioessays 24:690–695PubMedCrossRefGoogle Scholar
  83. Urakami S, Igawa M, Shirakawa H, Shiina H, Kawanishi M (1997) Quantitative analysis of NM23 protein immunoreactivity in renal cell carcinoma using an image analyzer. J Urol 157:1928–1931PubMedCrossRefGoogle Scholar
  84. Uv A, Cantera R, Samakovlis C (2003) Drosophila tracheal morphogenesis: intricate cellular solutions to basic plumbing problems. Trends Cell Biol 13:301–309PubMedCrossRefGoogle Scholar
  85. Wagner PD, Steeg PS, Vu ND (1997) Two-component kinase-like activity of nm23 correlates with its motility-suppressing activity. Proc Natl Acad Sci USA 94:9000–9005PubMedCrossRefGoogle Scholar
  86. Wallet V, Mutzel R, Troll H, Barzu O, Wurster B, Veron M, Lacombe ML (1990) Dictyostelium nucleoside diphosphate kinase highly homologous to Nm23 and Awd proteins involved in mammalian tumor metastasis and Drosophila development. J Natl Cancer Inst 82:1199–1202PubMedCrossRefGoogle Scholar
  87. Woolworth JA, Nallamothu G, Hsu T (2009) The Drosophila metastasis suppressor gene Nm23 homolog, awd, regulates epithelial integrity during oogenesis. Mol Cell Biol 29:4679–4690PubMedCrossRefGoogle Scholar
  88. Wu M, Pastor-Pareja JC, Xu T (2010) Interaction between Ras(V12) and scribbled clones induces tumour growth and invasion. Nature 463:545–548PubMedCrossRefGoogle Scholar
  89. Xu J, Liu LZ, Deng XF, Timmons L, Hersperger E, Steeg PS, Veron M, Shearn A (1996) The enzymatic activity of Drosophila AWD/NDP kinase is necessary but not sufficient for its biological function. Dev Biol 177:544–557CrossRefGoogle Scholar
  90. Yamanaka T, Horikoshi Y, Sugiyama Y, Ishiyama C, Suzuki A, Hirose T, Iwamatsu A, Shinohara A, Ohno S (2003) Mammalian Lgl forms a protein complex with PAR-6 and aPKC independently of PAR-3 to regulate epithelial cell polarity. Curr Biol 13:734–743PubMedCrossRefGoogle Scholar
  91. Zhang Q, McCorkle JR, Novak M, Yang M, Kaetzel DM (2011) Metastasis suppressor function of NM23-H1 requires its 3′–5′ exonuclease activity. Int J Cancer 128:40–50PubMedCrossRefGoogle Scholar

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© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Department of MedicineBoston University School of MedicineBostonUSA

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