nm23-H_1基因突变对人高转移大细胞肺癌细胞株L9981经典Wnt信号通路调控机制的影响
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摘要
研究背景与目的：肺癌的侵袭和转移是肺癌的恶性标志和特征，也是导致肺癌患者治疗失败和死亡的主要原因。肺癌的侵袭和转移是一个多因素作用、多基因参与、涉及细胞多个信号通路改变，并经过多个阶段才最终形成的复杂生物过程。因此，探讨肺癌侵袭转移相关细胞信号传导通路的变化，不仅有助于揭示肺癌侵袭转移的分子机制，而且将为阻断肺癌侵袭转移的信号传导和逆转肺癌侵袭转移表型提供新的靶点和途径。我们的前期研究工作已经证明肿瘤转移抑制基因nm23-H_1的低表达、杂合性缺失和突变与肺癌的高转移性和预后不良有密切关系，并在调控“肺癌转移抑制级联”中发挥上游关键基因的作用。人高转移大细胞肺癌细胞株L9981中转染野生型nm23-H_1基因后，nm23-H_1可通过调控“肺癌转移抑制级联”中多个转移相关基因的表达，逆转肺癌细胞的转移表型。nm23-H_1基因对“肺癌转移抑制级联”的调控作用可能是通过细胞
Background and objectives: Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the patients with lung cancer. It is a complex biological behavior that associated with many factors, genes, signal pathways and processes. Therefore, to explore the changes of cell signal transduction related to invasion and metastasis in lung cancer will not only illuminate the molecular mechanism of tumor invasion and metastasis, but also provide a new targeting molecule and route for blocking signal transduction and reversing metastatic phenotype of lung cancer. Our previous researching works have proved that low expression and hetero-deletion of tumor metastasis suppressor gene nm23-H_1 was closely correlated with the high metastasis ability and poor prognosis of patient with lung cancer. nm23-H_1 gene is a key and
Background and objectives: Tumor metastasis is not only the malignant marker and characteristics of lung cancer, but also the main cause of failure to cure and lose their life of the patients with lung cancer. It is a complex biological behavior that associated with many factors, genes, signal pathways and processes. Therefore, to explore the changes of cell signal transduction related to invasion and metastasis in lung cancer will not only illuminate the molecular mechanism of tumor invasion and metastasis, but also provide a new targeting molecule and route for blocking signal transduction and reversing metastatic phenotype of lung cancer. Our previous researching works have proved that low expression and hetero-deletion of tumor metastasis suppressor gene nm23-H_1 was closely correlated with the high metastasis ability and poor prognosis of patient with lung cancer. nm23-H_1 gene is a key and
引文
1. Chambers AF, Matrisian LM. Changing views of the roleof matrix metalloproteinases in metastasis. J Natl Cancer Inst, 1997, 89 (17): 1260-1270.
2. Mulshine JL, Treston AM, Brown PH, et al. Initiators and promoters of lung cancer. Chest, Jan 1993; 103(1 Suppl): 4S-11S.
3．周清华，孙燕主编．肺癌新理论新技术进展．四川大学出版社，2003年12月第1版，90-110
4. Steeg PS, Bevilacqua G, Kopper L, et al. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst. 1988; 80(3): 200-204.
5. Steeg PS, Cohn KHand Leone A. Tumor metastasis and nm23: current concepts. Cancer Cells. Jul 1991; 3(7): 257-62
6．周清华，陈军，刘伦旭，等．nm23-H1基因缺失与人非小细胞肺癌转移相关性研究，中国胸心血管外科临床杂志，1998：5(3)：131-134
7．周清华，车国卫，覃杨，等．nm23-H1逆转肺癌转移表型及其分子机制实验研究．中国肺癌杂志．2003．6(2)：141-143
8．周清华，王艳萍，车国卫，等．人大细胞肺癌细胞系NL9980和L9981的建立及其生物学特性研究．中国肺癌杂志，2003，6(6)：464-468
9．付军科，周清华，朱文，等．nm23-H1基因能上调人肺癌细胞株L9981中GSK-3β激酶活性．中国肺癌杂志，2004，7(2)：89-94．
10. Ali A. Hoeflich KP, and Woodgett JR. Glycogen synthase kinase-3: properties, functions, and regulation. Chem. Rev, 2001, 101, 2527-2540.
11. de la Rosa A, Williams RL, Steeg PS.nm23/nucleoside diphosphate kinase: toward a structural and biochemical understanding of its biological functions.Bioessays. 1995 Jan;17(1):53-62.
12. Paul D. Wagner, Ngoc-Diep Vu. Phosphorylation of ATP-Citrate Lyase by Nucleoside Diphosphate Kinase. 1995;270:21758-21764
13. Jose M.P. Freije, Pilar Blay, et al. Site-directed Mutation of m23-H1. 1997; 272: 5525-5532
14. Engel M, Veron M, Theisinger B,et al. A novel serine/threonine-specific protein phosphor-transferase activity of nm23/nucleoside-diphosphate kinase. Eur. J. Biochem, 234:200-207
15. Nicholas J. MacDonald, Jose M. et al. Site-directed Mutagenesis of nm23-H 1. J.Biol.Chem. 1996; 271: 25107-25116
16. Huelsken J,Behrens J. The Wnt signaling pathway. J Cell Science 2002,115, 3977-3978
17. Biggs J, Hersperger E, Steeg PS, 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
18. Polakis P. Wnt signaling and cancer. Genes Dev 2000; 14: 1837-1851.
19. He X., Saint-Jeannet JP, Wang, Y, et al. A member of the Frizzled protein family mediating axis induction by Wnt-5A. Science 1997.275: 1652-1654.
20. Lee, F.S., Lane, T.F., Kuo, A., et al. Insertional mutagenesis identifies a member of the Wnt gene family as a candidate oncogene in the mammary epithelium of int-2/Fgf-3 transgeneic mice. Proc. Natl. Acad. Sci. 1995, 92: 2268-2272.
21. Nusse, R. and Varmus, H.E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 1982.31: 99-109.
22. Roelink, H., Wagenaar, E., Lopes da Silva, S., et al. Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain. Proc.Natl. Acad. Sci. 1990.87: 4519-4523.
23. Cui J. Zhou X, Liu Y K,et al. Wnt signaling in hepatocellular carcinoma: Analysis of mutation and expression of beta-catenin, T-cell factor-4 and glycogen synthase kinase 3-beta genes. J Gastroenterol. Hepatol. 2003; 18:280-287.
24. Clements W M, Wang J, Sarnaik A, et al. p-catenin mutation is a frequent cause of Wnt Pathway activation in gastric cancer. Cancer Res,2002,62:3503-3506.
25. Hommura F, Furuuchi K, Yamazaki K, et al. Increased expression of p-catenin predicts better prognosis in non small cell lung carcinomas. Cancer,2002,94(3):752-758
26. Li L. Yuan H., Xie W, et al. Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells. J. Biol. Chem. 1999b.274:129-134.
27. Seldin DC. and Leder P. Casein kinase II alpha transgenee-induced murine lymphoma: Relation to theileriosis in cattle. Science 1995.267: 894-897.
28. Song DH, Sussman DJ, and Seldin DC. Endogenous protein kinase CK2 (casein kinase II) participates in Wnt signaling in mammary epithelial cells. J. Biol. Chem. 2000. 275: 23790 - 23797
29. Willet K, Brink M, Woodard A. Casein kinase 2 associates with and phosphorylates dishevelled. EMBO J. 1997.16: 3089-3096.
30. Uematsu K, He Biao, You Liang, et al. Activation of the Wnt pathway in non small cell lung cancer: evidence of disheveled overexpression. Oncogene, 2003;22:7218-7221.
31. Dommguez I, Itoh K., and Sokol SY. Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos. Proc. Natl. Acad. Sci. 1995,92: 8498-8502.
32. He X. Saint-Jeannet JP, Woodgett JR., et al. Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos. Nature 1995.374: 617-623.
33. Hedgepeth CM, Deardorff MA, Rankin K, et al. Regulation of glycogen synthase kinase 3 and downstream Wnt signaling by axin. Mol. Cell Biol. 1999b, 19: 7147-7157.
34. Ikeda S, Kishida S, Yamamoto H, et al. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3β and β-catenin and promotes GSK-3β dependent phosphorylation of β-catenin. EMBO J. 1998,17: 1371-1384.
35. Itoh K, Krupnik VE, and Sokol SY. Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and beta-catenin. Curr. Biol. 1998,8: 591-594.
36. Li, L., Yuan, H., Weaver, C.D., et al. Axin and Fratl interact with dvl and GSK, bridging Dvl to GSK in Wnt- mediated regulation of LEF-1. EMBO J. 1999a,18: 4233-1240.
37. Nakamura, T., Hamada, F., Ishidate, T., et al. . Axin, an inhibitor of the Wnt signaling pathway, interacts with beta- catenin, GSK-3beta and APC and reduces the beta-catenin level. Genes Cells 1998a,3: 395-403.
38. Rubinfeld B, Albert 1, Porfiri E, et al. Binding of GSK3aβ to the APC-β-catenin complex and regulation of complex assembly. Science 1996,272: 1023-1026.
39. Yamamoto H, Kishida S, Kishida M, et al. Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3β regulates its stability. J. Biol. Chem. 1999,274: 10681-10684.
40. Thomas GM, Frame S, Goedert M, et al. A GSK3β-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett. 1999.458:247-251.
41. Salic A, Lee E, Mayer L, et al. Control of beta-catenin stability: Reconstitution of the cytoplasmic steps of the Wnt pathway in Xenopus egg extracts. Mol. Cell: 2000, 5: 523-532.
42. Rubinfeld B., Albert I., Porfiri E., et al. Binding of GSK3 to the APC—Catenin Complex and Regulation of Complex Assembly. Science, 1996; 272: 1023-1026.
43. Hart MJ, de los Santos R., Albert IN, et al. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol, 1998; 8(10): 573-581.
44. Ikeda S, Kishida M, Matsuura Y, et al. GSK-3 beta-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by beta-catenin and protein phosphatase 2A complexed with Axin. Oncogene, 2000; 19(4): 537-545.
45. Hart MJ, de los Santos R, Albert, et al. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr. Biol. 1998. 8: 573-581.
46. Ikeda. S., Kishida, S., Yamamoto, H., et al.. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3βand β-catenin and promotes GSK-3β-dependent phosphorylation of β-catenin. EMBO J. 1998, 17: 1371-1384.
47. Satoh S, Daigo Y, Furukawa Y, et al. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat. Genet. 2000; 24: 245-250.
48. Kawasaki Y, Sato R, Akiyama T. Mutated APC and Asef are involved in the migration of colorectal tumor cells. Nat Cell Biol, 2003, 5(3): 211-215.
49. Muller T, Bain G, Wang X, et al. Regulation of epithelial cell migration and tumor formation by β-catenin signaling. Exp Cell Res, 2002, 280(1)119-133.
50. Dempke W, Rie C, Grothey A, et al. Cyclooxygenase-2: a novel target for cancer chemotherapy. J Cancer Res Clin Oncol,2001,127(7):411-417.
51. Kenneth JL and Thomas DS.Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2~(-ΔΔCr) Method.METHODS.2001;25:402-408
52. Leone A, Flatow U, Uing CR., et al. Recuced tumor incidence metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell, 1991, 65 (1): 25-35
53. Kantor JD, Mccormick B, Steeg PS, et al. Inhibition of cell mortality after nm23 transfection of human and marine tumor. Cancer Res. 1993; 53(8): 1971-1973
54. Lacombe ML, Milon L, Munier A, et al. The human nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr. 2000;32(3):247-258.
55. Otero AS. nm23/nucleoside diphosphate kinase and signal transduction. J Bioenerg Biomembr 2000; 32:269-275
56. Hartsough MT, Steeg PS nm23/nucleoside diphosphate kinase in human cancers. J Bioenerg Biomembr 2000;32:301-308
57. Kimura N, Shimada N, Fukuda M, et al. Regulation of cellular functions by nucleoside diphosphate kinases in mammals. J Bioenerg Biomembr 2000;32:309-315
58. Postel EH, Berberich SJ, Rooney JW, et al. Human nm23/nucleoside diphosphate kinase regulates gene expression through DNA binding to nuclease-hypersensitive transcriptional elements. J Bioenerg Biomembr 2000;32:277-284
59. Lacombe ML, Milon L, Munier A, et al. The human nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr 2000;32:247-258
60. Postel EH. Multiple biochemical activities of nm23/NDP kinase in gene regulation. J Bioenerg Biomembr, 2003; 35(1):31-40
61. Lombardi D, Mileo AM. Protein interactions provide new insight into nm23/nucleoside diphosphate kinase functions. J Bioenerg Biomembr, 2003; 35(1)67-71.
62. Kraeft SK, Traincart F, Mesnildrey S, et al.. Nuclear localization of nucleoside diphosphate kinase type B (nm23-H2)in cultured cells, Exp. Cell Res. 1996; 227: 63-69
63. 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,
64. Lascu I, Gonin P. The catalytic mechanism of nucleoside diphosphate kinase. J Bioenerg Biomembr, 2000, 32(3): 237-246.
65. Godfried MB, Veenstra M, Vsluis P, et al. The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H_1 and nm23-H_2. Oncogene, 2002; 21(13): 2097-2101.
66. Hayer J, Engel M, Seifert M, et al. Overexpression of nm23-H_4 RNA in colorectal and renal tumors. Anticancer Res., 2001; 21(4A): 2821-2825.
67. Munier A, Serres C, Kann ML, et al. nm23/NDP kinases in human male gene cells: role in sperminogenesis and sperm motility? Exp Cell Res. 2003; 289(2): 295-306.
68. Dooley S, Seib T, Engel M, et al. Isolation and characterization of the human genomic locus coding for the putative metastasis control gene nm23-H1. Hum Genet 1994; 93(1): 63-66.
69．骆成玉，祝学光．nm23基因的研究近况及其临床应用前景．国外医学外科学分册，1995；22(1)：24
70. Leone A, Flatow U, VanHoutte K et al. 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 1993; 8: 2325-2333.
71. Bhujwalla Z, Aboagye E, Gilles R et al. nm23-transfected MDAMB-435 human breast carcinoma cells form tumors with altered phospholipid metabolism and pH: A 31P nuclear magnetic resonance study in vivo and in vitro. Magn Res Med 1999; 41: 897-903.
72. Russell R, Pedersen A, Kantor J et al. Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines. Br J Cancer 1998; 78: 710-717.
73. Fukuda M, Ishii A, Yasutomo Y et al. Metastatic potential of rat mammary adenocarcinoma cells associated with decreased expression of nucleoside diphosphate kinase/nm23: Reduction by transfection of NDP Kinase a isoform, an nm23-H2 gene homolog. Int J Cancer 1996; 65: 531-537.
74. Leone A, Flatow U, King CR et al. Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell 1991; 65: 25-35.
75. Baba H, Urano T, Okada K et al. 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 1995; 55: 1977-1981.
76. Parhar RS, Shi Y, Zou M et al. Effects of cytokine mediated modulation of nm23 expression on the invasion and metastatic behavior of B16F10 melanoma cells. Int J Cancer 1995; 60: 204-210.
77. Miele ME, Rosa ADL, Lee JH et al. Suppression of human melanoma metastasis following introduction of chromosome 6 is independent of NMEl (nm23). Clin Exp Metastasis 1997; 15:259-265.
78. Tagashira H, Hamazaki K, Tanaka N et al. Reduced metastatic potential and c-myc overexpression of colon adenocarcinoma cells (Colon 26 line) transfected with nm23-R2 rat nucleoside diphosphate kinase an isoform. Int J Mol Med 1998; 2: 65-68.
79. Miyazaki H, Fukuda M, Ishijima Y et al. Overexpression of nm23-H2/NDP Kinase B in a human oral squamous cell carcinoma cell line results in reduced metastasis, differentiated phenotype in the metastatic site, and growth factor-independent proliferative activity in culture. Clin Cancer Res 1999; 5: 4301-4307.
80. Lombardi D, Lacombe ML, and Paggi MG.nm23: unraveling its biological function in cell differentiation. J Cell Physiol. 2000; 182(2): 144-149.
81. 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(1):53-62.
82. Hartsough MT, Steeg PS.nm23/nucleoside diphosphate kinase in human cancers. J Bio-energ Biomembr. 2000;32(3):301-308.
83. Otero AS.nm23/nucleoside diphosphate kinase and signal transduction. J Bioenerg Biomembr. 2000;32(3):269-275.
84. Leone A, Flatow LI, King CR, et al. Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell. 1991;65(1):25-35.
85. Baba, H Urano T, Okada, K et al. Two isotypes of murine nm23/nucleoside diphosphate kinase, nm23-Ml and nm23-M2, are involved in metastatic suppression of a murine melanoma line. Cancer Research, 1995;55:1977-1981
86. Barnes R, Masood S, Barker E, et al. Low nm23 protein amonginfiltrating ductal breast carcinomas correlates with reduced patient survival. American J Pathology, 1991, 139: 245-250
87. Florenes VA, Aamdal S, Myklebost O, et al. Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. Cancer Res., 1992; 52:6088-6091.
88. Yamaguchi A, Urano T, Goi T, et al.. Expression of human nm23-H1 and nm23-H2 proteins in hepatocellular carcinoma.Cancer, 1994;73(9):2280-2284.
89. Nakayama T, Ohtsuru A, Nakao K, et al. Amonghuman hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product. J Natl Cancer Inst. 1992; 84(17):1349-I354.
90. Nakayama H, Yaqui W, Yokosuka H, et al. Reduced expression of nm23 is associated with metastasis of human gastric carcinomas. Jpn J Cancer Res. 1993; 84(2): 184-190.
91. Bertheau P, De La rosa A. Steeg PS, et al. nm23 protein in neoplasmtic and nonneoplasmtic thyroid tissues. Am J Patol, 1994; 145:26-32
92. Igawa M, Rukstalis DB, Tanabe T, et al. High levels of nm23 expression is related to cell proliferation in human prostate cancer.Cancer Res., Mar 1994; 54: 1313-1318.
93. Zou M, Shi Y,al-Sedairy S, et al. High levels of nm23 gene amongadvanced stage of thyroid carcinomas.Br J Cancer, 1993; 68(2): 385-288.
94. Kawakubo Y, Sato Y, Koh T, et al. Expression of nm23 protein in pulmonary adeno-carcinomas: inverse correlation to tumor progression. Lung Cancer, 1997:17(1): 103-113.
95. Engel M, Theisinger B, Seitz G, et al. High levels of nm23-H1 and nm23-H2 messenger RNA in human squamous cell lung carcinoma are associated with poor differentiation and advanced tumor stages. Int J Cancer, 1993,55(3):375-379
96. Ozeki Y, Takishima K, and Mamiya G Immunohistochemical analysis of nm23/NDP kinase amonghuman lung adenocarcinoma: association with tumor progression in Clara cell type. Jpn J Cancer Res, 1994; 85(8): 840-846.
97. Bertheau P, De La Rosa A, Steeg PS. et al. nm23 protein in neoplastic and non-neoplastic thyroid tissues. Am J Patol, 1994;145(1): 26-32.
98. Engel M, Theisinger B, Seib T,et al. High levels of nm23-H1 and nm23-H2 messenger RNA in human squamous-cell lung carcinoma are associated with poor differentiation and advanced tumor stages. Int J Cancer, 1993; 55(3): 375-379.
99. Volm M, Martern J, Koomagi R. Association between nm23-H_1 expression. Proliferation and apoptosis in non-small cell lung carcinoma. Clin Exp metastasis. 1998; 16(7): 596-602.
100．王海峰，陈晓峰，高文等．nm23mRNA表达与肺癌的分化转移及病理之间的相关性研究．中国临床医学，2004；11(2)：24-27
101. Huwer H, Engel M, Welter C, et al. Squamous cell carcinoma of the lung: does the nm23 gene expression correlate to the tumor stage? Thorac Cardiovasc Surg, 1994; 42(5): 298-301.
102．陈军，周清华，覃杨，等．人肺癌中nm23等位基因缺失的研究．中国肺癌杂志．2000；3(1)：8-13．
103. Lai Ww, Wu MH, Yan JJ, et al. Immunohistochemical analysis of nm23-H_1 in stage Ⅰ non-small cancer: a useful marker in prediction of metastases. Ann Thorac Surg. 1996. 62(5): 1500-1504.
104．陈琼．陈全群，李国虎．原发性肺癌nm23基因mRNA表达的研究．中国现代医学杂志．2001；11(4)：18-121
105. Ozeki Y. Takishima K, Mamiya G, et al. Immunohistochemical analysis of nm23/NDP kinase amonghuman lung adenocarcinoma: Association with tumor progression in clara cell type. Jpn J Cancer Res. 1994. 85(8): 840-845
106. Higashiyama M, Doi O, Yokouchi H., et al.. Immuunohistochemical analysis of nm23 gene product/NDP kinase amongpulmonary adenocarcinoma: Lack of prongnostic value. Br J Cancer. 1992, 63(2): 533.
107．陈晓峰，周清华，石应康．nm23与肺癌转移和预后关系的研究进展．中国胸心外科临床杂志．1997；4(2)：48-50
108．刘伦旭，覃扬，周清华，等．Northern印迹杂交分析nm23基因在人肺癌中的表达研究． 中华肿瘤杂志，1998，20(5)：342-344
109．雷文东，张汝刚，闫水忠，等．nm23基因在人肺癌中的表达及其与肺癌淋巴结转移的关系．中华肿瘤杂志，1994，16(4)：277-279
110. Kawakabo Y, Sato Y, Koh T, et al. Expression of nm23 protein in pulmonary adeno-carcinomas: inverse correlation to tumor progression. Lung Cancer, 1997, 17(1): 103-113.
111. Huwer H, Kalweit G, Engel M, et al. Expression of candidate tumor suppression gene nm23 in the bronchial system of patients with squamous cell lung cancer. European journal of cardio-thoracic surgery. 1997; 11 (2): 206-209
112. Wu WL, Ming HW, Jing JY, et al. Immunohistochemical Analysis of nm23-H1 in Stage Ⅰ Non-Small Cell Lung Cancer: A Useful Marker in Prediction of Metastases. Ann. Thorac. Surg., 1996; 62: 1500—1504.
113. Ohta Y, Nozaki Z, Nozawa H, et al. The predictive value of vascular endothelial growth factor and nm23 for the diagnosis of occult metastasis in non-small cell lung cancer. Jpn J Cancer Res, Mar 2001; 92(3): 361-6.
114. MacDonald NJ, De la Rosa A, Benedict MA, A serine phosphorylation of nm23, and not its nucleoside diphosphate kinase activity, correlates with suppression of tumor metastatic potential J. Biol. Chem., 1993; 268: 25780-25789.
115. Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. Annual Reviews in Cell and Development Biology, 1998, 14: 59-88.
116. Peifer M, Polakis P. Wnt signaling in onceogenesis and embryogenesis-a look outside the nucleus. Science 2000. 287: 1606-1609.
117. Kuhl M, Sheklahl LC, Park M, et al. The Wnt/Ca2~+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet 2000, 16: 279-283.
118. Peifer M, McEwen DG: The ballet of morphogenesis: unveiling the hidden choreographers. Cell 2002, 109:271-274.
119. Capdevila J, Belmonte JCI: Extracellular modulation of the Hedgehog, Wnt and TGF-β signaling pathways during embryonic development. Curr Opin Genet Dev 1999, 9:427-433.
120. Saneyoshi T, Kume S, Amasaki Y, et al. The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature 2002, 417:295-299.
121. Malbon CC, Wang H, Moon RT: Wnt signaling and hetertrimeric G-Proteins: strange bedfellows or a classic romance? Biochem Biophys Res commun 2001, 287:589-593.
122. Kuhi M, Geis K, Sheldahl LC, et al. Antagonistic regulation of convergent extension movements in Xenopus by Wnt/beta-catenin and Wnt/Ca~(2+) signaling. Mech Dev 2001, 106:61-76.
123. Winklbauer R, Medina A, Swain RK, et al. Frizzled-7 signaling controls tissue separation during Xenopus. Nature 2001,413:856-860.
124. Sokol S: Arole for Wnts in morphogenesis and tissue polarity. Nat Cell Biol 2000, 2:E124-E125.
125. Akiyama T., Wnt/beta-catenin signaling. Cytokine Growth Factor Rev. 2000.11: 273-282.
126. Tulac S, Nayak NR, Kao LC, et al. Identification, characterization, and regulation of the canonical Wnt signaling pathway in human endometrium. J Clin Endocrinol Metab, 2003, 88(8):3860 -3866.
127. Miller JR. Wnt signaling transduction .In: Alison M ed. The cancer handbook [M]. London: Nature Publushing Group, 2002:195 - 208.
128. Meirmanov S,NakashimaM, Rogounovitch T, et al. Small cell carcinoma of the endo-metrium: report of a case with analysis of Wnt/beta-catenin pathway. Pathol Res Pract, 2003, 199 (8): 551 -558.
129. Lustig B, Behrens J. The Wnt signaling pathway and its role in tumor development. Cancer Res Clin Oncol, 2003,129:199-221.
130. Kikuchi A. Tumor formation by genetic mutations in the components of the Wnt signaling pathway . Cancer Sci, 2003, 94(3): 225 - 229.
131. Clements WM, Lowy AM, Groden J. Adenomatous polyposis coli/beta-catenin interaction and downstream targets: altered gene amonggastrointestinal tumors.Clin Colorectal Cancer,2003, 3 (2): 113-120.
132. Li H, Pamukcu R, Thomp son WJ. beta2Catenin signaling: therapeutic strategies in oncology. Cancer Biol Ther, 2002,1(6):621-625.
133. Miao J, Kusafuka T, Okada A. Detection of a novel alteration of the Axin gene in various pediatric neoplasms. Oncol Rep, 2003, 10(6): 1943 -1946.
134. Wharton KA Jr. Runnin with the Dvl: proteins that associate with Dsh/Dvl and their significance to Wnt signal transduction .Dev Biol, 2003, 253 (1) : 1 - 17.
135. Peifer M, Polakis P. Wnt signaling in oncogenesis and embryo genesis/a look outside the nucleus. Science, 2000, 287: 1606 -9.
136. Waltzer L,BienzM. The control of beta - catenin and TCF during embryonic development and cancer. Cancer Metastasis Rev, 1999, 18: 231 - 246.
137. Kantor JD,McCormick B, Steeg PS, et al. Inhibition of cell mortility after nm23 transfection of human and murine tumor cells. Cancer Res, 1993; 53 (9):1971-1963.
138. Macdonald NJ ,DelaRosa A ,BenedictMA , et al. A serine phosphorylation of nm23 and not its nucleoside diphosphate kinase activity, correlatesw ith supp ression of tumor metastatic potential. J Biol Chem, 1993;268(34):25780- 25789.
139. Korinek V, Barker N, Moerer P, et al.. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4, Nat. Genet. 1998; 19: 379-383.
140. Brennan KR, Brown AM, Wnt proteins in mammary development and cancer, J. Mammary Gland Biol. Neoplasia 2004; 9: 119-131.
141. Pandur P, Lasche M, Eisenberg LM, Kuhl M. Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis, Nature, 2002; 418: 636-641.
142. Reya T, Duncan AW, Ailles L, et al.. A role for Wnt signalling in self-renewal of haematopoietic stem cells, Nature 2003; 423: 409-414.
143. Rijsewijk F, Schuermann M, Wagenaar K, et al.. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless, Cell 1987; 50: 649-657.
144. Morrisey KK, Wnt signaling and pulmonary fibrosis, Am. J. Pathol. 2003; 162: 1393-1397.
145. Yamaguchi TP, Bradley A, McMahon AP, et al. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo, Development 1999: 126: 1211-1223.
146. Weidenfeld J, Shu W, Zhang L, et al.. The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium, J. Biol. Chem. 2002; 277: 21061-21070.
147. Li C, Xiao J, Hormi K, et al.. Wnt5a participates in distal lung morphogenesis, Dev. Biol. 2002; 248: 68-81.
148. Shu W, Jiang YQ, Lu MM, et al.. Wnt7b regulates mesenchymal proliferation and vascular development in the lung, Development 2002; 129: 4831-4842.
149. Bonnet AE, Lemon WJ, You M, Gene expression signatures identify novel regulatory pathways during murine lung development: implications for lung tumorigenesis, J. Med. Genet, 2003; 40: 408-417.
150. Chilosi M, Poletti V, Zamo A, et al.. Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis, Am. J. Pathol. 2003; 162: 1495-1502.
151. Hommura F, Furuuchi K, Yamazaki K, et al.. Increased expression of beta-catenin predicts better prognosis in nonsmall cell lung carcinomas, Cancer 2002; 94: 752-758.
152. Retera JM, Leers MP, Sulzer MA, et al.. The expression of beta-catenin in non-small-cell lung cancer: a clinicopathoiogical study, J. Clin. Pathol. 1998; 51: 891-894.
153. Kase S, Sugio K, Yamazaki K, et al.. Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance, Clin. Cancer Res. 2000; 6: 4789-4796
154. Sunaga N, Kohno T, Kolligs FT, et al. Constitutive activation of the Wnt signaling pathway by CTNNB1 (beta-catenin) mutations in a subset of human lung adenocarcinoma. Genes Chromosomes Cancer, 2001; 30(3): 316-321.
155. Shigemitsu K, Sekido Y, Usami N, et al.. Genetic alteration of the beta-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion, Oncogene 2001; 20: 4249-4257.
156. Nakatani Y, Masudo K, Miyagi Y. et al.. Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules, Mod. Pathol. 2002; 15: 617-624.
157. Uematsu K, He Biao, You Liang, et al. Activation of the Wnt pathway in non small cell lung cancer: evidence of disheveled overexpression. Oncogene, 2003, 23: 7218-7221.
158. Hommura F, Furuuchi K, Yamazaki K, et al. Increased expression of β-catenin predicta better prognosis in non-small cell lung carcinomas. Cancer 2002; 94: 752-758
159．付军科，周清华，朱文，等．nm23-H_1基因转染对人高转移大细胞肺癌细胞株L9981中β-catenin表达的影响．中国肺癌杂志．2004；7(6)：471-474
160. Rosengard AM, Krutzsch HC, Shearn A,et al.Reduced nm23/Awd protein in tumour metastasis and aberrant Drosophila development.Nature, 1989; 342(6246): 177-180.
161. Keith WN. From stem cells to cancer: balancing immortality and neoplasia, Oncogene 23 (2004) 5092-5094.
162. T. Reya, A.W. Duncan, L. Allies, J. Domen. D.C. Scherer, K. Willert, et al., A role for Wnt signalling in self-renewal of haematopoietic stem cells, Nature 423 (2003) 409-414.
163. Sato N, Meijer L, Skaltsounis L,et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3 -specific inhibitor, Nat. Med. 10 (2004) 55-63.
164. Ross SE , Hemati N , Longo KA , et al . Inhibition of adipogenesis by Wnt signaling. Science , 2000 , 289 (5481): 950-953
165. Reya T, OpRiordan M, Okamura R, et al. Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism. Immunity , 2000 ,13(1): 15-24
166. Cherui A , Walsh C A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science , 2002 , 297 (5580): 365-369
167. Chenn A , Walsh C A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science , 2002 , 297 (5580): 365-369
168. Jamieson CH, Allies LE,.Dylla SJ,, et al., Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML, N. Engl. J. Med. 2004,351:657-667.
169. Leone A, McBride OW, Weston A, et al. Somatic allelic deletion of nm23 in human cancer. Cancer Res, 1991 ,51(9) : 2490-2493.
170. Cohn KH, Wang FS, Desoto-lapaix F, et al. Association of nm23-H1 allelic deletions with distant metastasis in colorectal carcinoma. Lancet, 1991,338(8769):722-724.
171. Wang L, Patel U, Ghosh L, et al. Mutation in the nm23 gene is associated with metastasis in colorectal cancer. Cancer Res, 1993, 53(4): 717-720.
172．周清华，陈军，孙芝琳，等．nm23-H1等位基因缺失与人非小细胞肺癌转移相关性研究．中国胸心血管外科临床杂志 1998，5(3)：131-134
173．刘伦旭，周清华，孙芝琳等．人肺癌组织中nm23-H_1基因突变研究．中国肺癌杂志．2000；3(3)：201-204
174．汪家政，范明主编．蛋白质技术手册．科学出版社．2000年8月 第一版：42-47．
175. Willert K, Nusse R, Beta-catenin: a Key mediator of Wnt signaling. Curr Opin Genet Dev, 1999, 18(55): 7860-7872.
176. Rubinfeld B, Albert I, Porfiri E, et al. Binding of GSK3 to the APC—Catenin Complex and Regulation of Complex Assembly Science, 1996; 272: 1023-1026.
177. Behrens J, Jerchow BA, Wartele M, et al. Functional Interaction of an Axin Homolog, Conductin, with β-Catenin, APC, and GSK3β. Science, 1998: 280(5365): 596-599
178. Miyoshi Y, Ando H, Nagase H, et al. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc Natl Acad Sci USA, 1992, 8(1): 4452-4456.
179. Sansom OJ, Reed KR, Hayes AJ, et al. Loss of APC in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev. 2004, 18(12): 1385-1390.
180 Woodgett JR. Molecular coloning and expression of glycolgen synthase kinase-3/factor A. EMBO J, 1990, 9(8): 2431-2438.
181 Woodgett JR. cDNA clonging and propertyes of glycolgen synthase kinase-3. Methods Enzymol, 1991, 200: 564-577.
182. Yamamoto H, Kishida S, Kishida M, et al. Phosphorylation of axin, a Wnt signal negative regulator, by glycolgen synthase kinase-3beta regulates its stability. J Biol Chem, 1999, 274(16): 10681-10684.
183. Kishida S, Yamamoto H, Ikeda S. et al. Axin a negative regulator of the Wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stblization of beta-catenin. J Biol Chem, 1998,273(18): 10823-10826.
184. Luo W, Lin SC. Axin: a master scaffold for multiple signaling pathways. Neurosignals, 2004,13(3):99-113
185. Aoki M, Hecht A, Kruse U, et al. Nuclear endpoint of Wnt signaling: neoplasmtic transformation induced by transactivating lymphoid-enhancing factor 1. Proc Natl Acad Sci USA, 1999,96(1): 139-144.
186. Nelson WJ, Nusse R. Convergence of Wnt, (3-catenin and cadherin pathways. Science, 2004,303(5663):1483-1487.
187. Novak A, Hsu SC, Hagestein CL. et al. Cell adhesion and the intergin linked kinase regulated the LEF-1 and beta-catenin signaling pathways . Pro. Natl. Acad Sci.USA , 1998 ,95(8): 4374-4379.
188. Elizabeth P. How a Growth Control Path Takes a Turn to Cancer. Science, 1998, 281(5382): 1438-1441.
189. Chie S, Joseph BW, and Lweis TW. Bridging of beta-catenin and glycogen synthase kinase-3beta by Axin and inhibition of beta-catenin-mediated transcription. Proc. Natl. Acad. Sci. USA , 1998 ,95(6) :3020-3023.
190. Roose J, Gerwitn H, Moniek VB, et al. Synergy Between Tumor Suppressor APC and the beta-catenin/Tcf4 Target Tcfl. Science ,1999 ,285(5435) :1923-1926.
191. Easwaran V , Pish VM, Salimuddin BS. Cross-regulation of beta-caternin-LEF/ TCF and retinoid signaling pathways.Curr Biol, 1999 ,9(23) M415-1418.
192. Embi N, Rylatt D B, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMPdependent protein kinase and phosphorylase kinase. Eur J Biochem, 1980, 107: 519-527.
193.Woodgett JR, Cohen P. Multisite phosphorylation of glycogensynthase: molecular basis for the substrate specificity of glycogen synthase kinase-3 and casein kinase-II (glycogen synthase kinase-5). Biochim Biophys Acta, 1984, 788 : 339-347.
194. Ishiguro K, Shiratsuchi A, Sato S,et al.Glycogen synthase kinase 3 beta is identical to tau protein kinase I generating several epitopes of paired helical filaments. FEBS Lett, Jul 1993; 325(3): 167-72.
195. Embi, N. Rylatt, DB. and Cohen, P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur. J. Biochem. 1980; 107,519-527.
196. Woodgett, JR. and Cohen, P. Multisite phosphorylation of glycogen synthase. Molecular basis for the substrate specificity of glycogen synthase kinase-3 and casein kinase-II (glycogen synthase kinase-5). Biochim. Biophys. Acta 1984;788,339 -347.
197. Frame S, Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem J, 2001,359: 1-16
198. Grimes C A, Jope R S. The multifaceted roles of glycogen synthase kinase 3b in cellular signaling.Prog Neurobiol, 2001,6 5: 391-426
199. Woodgett J R. Judging a protein by more than its name: GSK-3. Sci STKE, 2001, 100: RE12
200. Woodgett J R.Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J, 1990, 9 : 2431-2438
201. Woodgett, JR. Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J. 1990;9:2431 -2438.
202. Ali A. Hoeflich KP and Woodgett JR. Glycogen synthase kinase-3: properties, functions, and regulation. Chem. Rev. 2001; 101,2527 -2540.
203. Adnan Ali, Klaus P, and James R.W. Glycogen synthase kinase-3: properties, function and regulation. Chem. Rev.2001, 101: 2527-2540.
204. Gould TD, Zarate CA, and Manji HK. Glycogen synthase kinase-3: A target for novel bipolar disorder treatments. J Clin Psychiatry 2004:65, 10-21.
205. Frame S. and Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem. J. 2001;359,l-16.
206. Bax B, Carter PS, Lewis C, et al. The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation. Structure (Camb) 2001 ;9,1143 -1152.
207. Dajani R, Fraser E, Roe S. et al. Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell.2001;105,721 -732.
208. ter Haar E, Coll JT, Austen DA, Structure of GSK3beta reveals a primed phosphorylation mechanism. Nat. Struct. Biol. 2001 ;8, 593-596.
209. Frame S and Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem. J. 2001; 359,1 -16
210. Thomas, GM, Frame S, Goedert M, et al.A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett. 1999;458,247-251.
211. Dajani R, Fraser E, Roe SM,et al. Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 2001;105,721-732.
212. Hartigan,JA, Johnson,GV. Transient increases in intracellular calcium result in prolonged site-selective increases in Tau phosphorylation through a glycogen synthase kinase 3β-dependent pathway.J Biol Chem, 1999, 274,21395-21401.
213. Cross D A E, Alessi D R, Cohen P. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.Nature, 1995, 378: 785-789.
214. Shaw M, and Cohen P.Role of protein kinase B and the MAP kinase cascade in mediating the EGF-dependent inhibition of glycogen synthase kinase 3 in Swiss 3T3 cells. FEBS Lett.1999, 461, 120-124.
215. He X, Saint-Jeannet J.P, Woodgett J.R, et al. Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos. Nature, 1995, 374, 617-622.
216. Troussard AA, Tan C, Yoganalhan TN,et al.Cell-extracellular matrix interaction stimulate the Ap-1 transcription factor in an intergrin-linked kinase and glycogen synthase kinase 3-dependent manner.Mol Cell Biol, 1999,19:7420-7427.
217. Bhat RV, Shanley J, Correll MP, et al. Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3beta in cellular and animal models of neuronal degeneration. Proc. Natl. Acad. Sci. USA 2000;97,11074 -11079
218. Bijur GN and Jope RS. Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3 beta. J. Biol. Chem. 2001;276,37436 -37442.
219. Morisco C, Seta K, Hardt SE, et al. Glycogen synthase kinase 3Γ regulates GATA4 in cardiac myocytes. J Biol Chem.2001;276:28586-28597.
220. Haq S, Choukroun G, Kang ZB,et al. Glycogen synthase kinase-3Γ is a negative regulator of cardiomyocyte hypertrophy. J Cell Biol. 2000; 151:117-130.
221. Diehl JA, Cheng M, Roussel MF, et al.Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellutar localization. Genes Dev. 1998; 12: 3499-3511.
222. Bijur GN, Jope RS. Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3(?). J Biol Chem. 2001; 276: 37436-37442.
223. Sheelagh F, Philip C.GSK3 takes center stage more than 20 years after its discovery. Biochem J, 2001, 359, 1-16.
224. Gautam N, Richard S. Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3β. The Journal of Biological Chemistry, 2001, 276: 37436-37442.
225．付军科，周清华，朱文等。nm23-H1基因转染能上调人肺癌细胞株L9981中GSK-3β激酶活性．中国肺癌杂志，2004；7(4)：81-85
226. Miller. J. R. The Writs. Genome Biol. 2002, 3: 3001.
227. Smalley MJ. and Dale TC. Wnt signalling in mammalian development and cancer. Cancer Metastasis Rev. 1999; 18, 215-230.
228. Lako M, Strachan T, Bullen P, et al. Isolation, characterisation and embryonic expression of WNT11, a gene which maps to 11q13.5 and has possible roles in the development of skeleton, kidney and lung. Gene, 1998; 219(1-2): 101-10.
229. Huelsken J and Behrens J. The Writ signalling pathway. J. Cell Sci. 2002; 115, 3977-3978.
230. Seidensticker MJ. and Behrens J. Biochemical interactions in the Wnt pathway. Biochim. Biophys. Acta 2000; 1495, 168-182.
231. Tejpar S, Cassiman JJ, van Cutsem E. The molecular basis of colorectal cancer. Acta Gastro-enterol Belg, 2001, 64 (3): 249-254.
232. van de WeteringM, Sancho E, Verweij C, et al. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002, 111 (2): 241-250.
233. D'Orazio D, Muller PY, Heinimann K, et al. Overexpression of Wnt target genes in adenomas of familial adenomatous polyposis patients. Anticancer Res, 2002; 22 (6A):3409-3414.
234. Ginger RS, Dalton EC, Ryves WJ, et al. Glycogen synthase kinase-3 enhances nuclear export of a dictyostelium STAT protein. EMBO J. 2000;19:5483-5491.
235. Cohen P, Frame S. The renaissance of GSK3. Nat Rev Mol Cell Biol.2001;2:769-776.
236. Peifer M, Polakis P. Wnt signaling in oncogenesis and embryogenesis——a look outside the nucleus. Science ,2000 ,287 :1606—1609
237. Hinoi, T., Yamamoto, H., Kishida, M., et al.. Complex formation of adenomatous polyposis coli gene product and axin facilitates glycogen synthase kinase-3 beta-dependent phosphorylation of beta-catenin and down-regulates beta-catenin. J. Biol. Chem. 2000; 275,34399 -34406
238. Ikeda S, Kishida S, Yamamoto H, et al.Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 1998;17,1371 -1384.
239. Jho E, Lomvardas S and Costantini F. A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression. Biochem. Biophys. Res. Commun 1999;266,28-35.
240. Yamamoto H, Kishida S, Kishida M, et al.Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability. J. Biol. Chem. 1999;274,10681 -10684.
241. Rubinfeld B, Albert I, Porfiri E, et al. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 1996; 272,1023 -1026.
242. Kim L, Kimmel AR. GSK3, a master switch regulating cell-fate specification and tumor-igenesis. Curr Opin Genet Dev. 2000; 10:508-514.
243. Imahori K, Uchida T. Physiology and pathology of tau protein kinases in relation to Alzheimer's disease. J Biochem (Tokyo). 1997;121:179-188.
244. Miller JR, Hocking AM, Brown JD, Moon RT. Mechanism and function of signal transduction by the Wnt/βcatenin and Wnt/Ca2p pathways.Oncogene. 1999; 18:7860-7872.
245. Fiol CJ, Mahrenholz AM, Wang Y, Roeske RW, Roach PJ. Formation of protein kinase recognition sites by covalent modification of the substrate: molecular mechanism for the synergistic action of casein kinase II and glycogen synthase kinase 3. J Biol Chem. 1987;262:14042-14048.
246. Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR. Glycogen synthase kinase-3: functions in oncogenesis and development. Biochim Biophys Acta. 1992; 1114:147-162.
247. Porter CM, Havens MA, Clipstone NA. Identification of amino acid residues and protein kinases involved in the regulation of NFATc subcellular localization. J Biol Chem. 2000;275:3543-3551.
248. ter Haar E, Coll JT, Austen DA, Hsiao HM, Swenson L, Jain J. Structure of GSK3Γ reveals a primed phosphorylation mechanism. Nat Struct Biol. 2001;8: 593-596.
249. Woods YL, Cohen P, Becker W, Jakes R, Goedert M, Wang X, Proud CG The kinase DYRK phosphorylates protein-synthesis initiation factor elF2B- at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase. Biochem J. 2001 ;355:609-615.
250. Amit S, Hatzubai A, Birman Y,et al. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev. 2002;16,1066 -1076.
251. Hagen T, di Daniel E, Culbert AA.et al. Expression and characterization of GSK-3 mutants and their effect on beta-catenin phosphorylation in intact cells. J. Biol. Chem. 2002:277,23330 -23335.
252. Hagen T. and Vidal-Puig A. Characterisation of the phosphorylation of beta-catenin at the GSK-3 priming site Ser45. Biochem. Biophys. Res. Commun. 2002;294,324 -328.
253. Liu C, Li Y, Semenov M, et al.Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 2002; 108,837 -847.
254. Sakanaka C. Phosphorylation and regulation of beta-catenin by casein kinase I epsilon. J. Biochem. (Tokyo) 2002; 132,697 -703.
255. Yanagawa S, Matsuda Y, Lee JS. Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila.2002;EMBO J. 21,1733 -1742.
256. Schwarz-Romond T, Asbrand C, Bakkers J,et al. The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling. Genes Dev. 2002; 16,2073 -2084.
257. Farr GH, 3rd, Ferkey DM, Yost C,et al. Interaction among GSK-3, GBP, axin, and APC in Xenopus axis specification. J. Cell Biol. 2002; 148,691 -702.
258. Ferkey DM and Kimelman D. Glycogen synthase kinase-3 beta mutagenesis identifies a common binding domain for GBP and Axin. J. Biol. Chem. 2002;277,16147 -16152.
259. Fraser E, Young N, Dajani R,et al. Identification of the Axin and Frat binding region of glycogen synthase kinase-3. J. Biol. Chem. 2002;277,2176 -2185.
260. Sumoy L, Kiefer J and Kimelman D. Conservation of intracellular Wnt signaling components in dorsal-ventral axis formation in zebrafish. Dev. Genes Evol. 2002;209, 48-58.
261. Yost C, Farr GH, 3rd, Pierce SB,et al. GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis. Cell 1998;93,1031 -1041.
262. Thomas GM, Frame S, Goedert M,et al. A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett. 1999; 458, 247-251.
263. Franca-Koh J, Yeo M, Fraser E, et al. The regulation of glycogen synthase Kinse-3 nuclear export by Frat/GBP. J. Biol. Chem. 2002; 277, 43844-43848.
264. Ding VW, Chen RH and McCormick E Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling. J. Biol. Chem. 2000; 275, 32475-32481.
265. Yuan H, Mao J, Li L. et al. Suppression of glycogen synthase kinase activity is not sufficient for leukemia enhancer factor-1 activation. J. Biol. Chem. 1999; 274, 30419-30423.
266．王瑞年．Wnt信号传导与癌症．中国肿瘤，2002；11(10)：594-596．
267. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenolmenon with wide ranging implicateons in tissue kinetics. Br J Cancer. 1972, 26: 239-257
268. Stetler-Stevenson WG, Aznavoorian S, and Liotta LA. Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol, 1993; 9: 541-73.
269. Gilles AM , Presecan E, Vonica A et al. Nucleoside diphosphate kinase from human erythrocytes: Structural characterization of the two polypeptide chains respondible for heterogeneity, of hexameric enzyme. J Biol Chem, 1991; 266: 8784
270. You L. He B, Xu Z, et al.. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells, Oncogene 2004; 23: 6170-6174.
271．车国卫，周清华，朱文等．nm23-H1基因逆转人高转移大细胞肺癌细胞L9981转移表型的分子机制．癌症，2005，24(3)：278—284
272．高庆蕾，马丁．nm23-H_1基因表达与卵巢转移的相关性．癌症．2004；23(6)：650—654
273. Leone A, Flatow U, VanHoutte K et al. 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 1993; 8: 2325-2333.
274. Bhujwalla Z, Aboagye E, Gilles R et al. nm23-transfected MDAMB-435 human breast carcinoma cells form tumors with altered phospholipid metabolism and pH: A 31P nuclear magnetic resonance study in vivo and in vitro. Magn Res Med 1999; 41: 897-903.
275. Russell R, Pedersen A, Kantor J et al. Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines. Br J Cancer 1998; 78: 710-717.
276. Fukuda M, Ishii A, Yasutomo Y et al. Metastatic potential of rat mammary adenocarcinoma cells associated with decreased expression of nucleoside diphosphate kinase/nm23: Reduction by transfection of NDP Kinase a isoform, an nm23-H2 gene homolog. Int J Cancer 1996; 65: 531-537.
277. Leone A, Flatow U, King CR et al. Reduced tumor incidence,metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell 1991; 65: 25-35.
278. Baba H, Urano T, Okada K et al. Two isotypes of murine nm23/Nucleoside Diphosphate Kinse, nm23-M1 and nm23-M2, are involved in metastatic suppression of a murine melanoma line. Cancer Res 1995; 55: 1977-1981.
279. Parhar RS, Shi Y, Zou M et al. Effects of cytokine mediated modulation of nm23 expression on the invasion and metastatic behavior of B16F10 melanoma cells. Int J Cancer 1995; 60: 204-210.
280. Miele ME, Rosa ADL, Lee JH et al. Suppression of human melanoma metastasis following introduction of chromosome 6 is independent of NMEl (nm23). Clin Exp Metastasis 1997; 15:259-265.
281. Tagashira H, Hamazaki K, Tanaka N et al. Reduced metastatic potential and c-myc overexpression of colon adenocarcinoma cells (Colon 26 line) transfected with nm23-R2 rat nucleoside diphosphate kinase a isoform. Int J Mol Med 1998; 2: 65-68.
282. Miyazaki H, Fukuda M, Ishijima Y et al. Overexpression of nm23-H2/NDP Kinase B in a human oral squamous cell carcinoma cell line results in reduced metastsis, differentiated phenotype in the metastatic site, and growth factor-independent proliferative activity in culture. Clin Cancer Res 1999; 5: 4301-4307.
283. Liotta LA. Tumor invasion and metastases: role of the basement membrane. Am J Pathol, 1986, 117: 339-348.
284. Albini A, Iwamoto Y, Kleinman HK, et al. A rap id in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res, 1987, 47: 3239-3245.
285．周清华，王艳萍、车国卫等．人大细胞肺癌细胞系NL9980和L9981的建立及其生物学特性研究．中国肺癌杂志．2003；6(6)：464-468
286．车国卫，周清华，王艳萍等．人肺癌细胞株L9981-nm23-H1的建立．中国肺癌杂志．2004，7(3)：187-189
287. Liotta LA. Cancer cell invasion and metastasis. Scientific American, 1992, 266(2): 34—41.
288. Liotta LA, Rao CN, Barsky SH. Tumor invasion and the extracellular matrix. Lab Invest. 1983; 49(6): 636-49.
289. Hand PH, Thor A, Schlom J, Expression of laminin receptor in normal and carcinomatous human tissues as defined by a monoclonal antibody. Cancer Res., 1985; 45: 2713-2719.
290. Turner S, Sherratt JA. Intercellular adhesion and cancer invasion: a discrete simulation using the extended Potts model. J Therol Biol, 2002; 216: 85-100.
291. Bremnes RM, Veve R, Hirsch FR, et al. The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastsis, and prognosis. Lung Cancer, 2002, 36: 115-124.
292．付军科，周清华，朱文，等．转染nm23-H1基因靶向阻断人大细胞肺癌细胞株L9981 Wnt 信号传导通路．中国肺癌杂志．2004；7(4)：294-297
293．郑海霞，申尔兰，周清华等．nm23-H1基因逆转肺癌细胞转移表型的功能鉴定．北京大学学报(医学版)．2005；37(3)：335—336
294. Guo HB, Liu F, Zhao JH, et al. Down-regulation of N-acetylglucosaminyl transferase Ⅴ by tumorigenesis or metastasis suppressor gene and its relation to metastatic potential of human hepatocarcinoma cells. J Cell Biochem, 2000, 79: 370-385
295. Kantor JD, McCormick B, Steeg PS, et al. Inhibition of cell motility after nm23 transfection of human and murine tumor cells. Cancer Res. 1993; 53: 1971-1973.
296. Nickerson JA, Wells WW. The microtubule-associated nucleoside diphosphate kinase. J Biol Chem, 1984, 259(18): 11297-11300.
297. Leone A, Flatow U, King CR. Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell, 1991; 65(1): 25-35.
298. Liotta LA, Steeg PS. Clues to the function of nm23 and Awd proteins in development, signal transduction and tumor metastasis provided by studies of dictyostelium discoideum. J Natl Cancer Inst, 1990, 82(14): 1170-1172.
299. Golden A, Benedict M, Shearn A, et al. Nucleoside diphosphate kinase, nm23 and tumor metastasis: possible biochemical mechanisms. In: Benz C, Liu E eds. Oncogenes and Tumor Sppressor Genes in Human Malignancies. Kluwr Academic Phblishers, 1993. 345-358.
300. Gilles AM, Presecan E, Vonica A, et al. Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J. Biol. Chem. 1991; 266: 8784-8789.
301．周清华，车国卫，覃扬，等．nm232H1基因逆转肺癌转移表型及其分子机制的实验研究． 中国肺癌杂志，2003；6(2)：141-143．
302. Bogenrieder T, Herlyn M. Axis of evil: molecular mechanisms of cancer metastasis. Oncogene, 2003, 22 (42): 6524-6536
1. Smith W, Khuri FR, The care of the lung cancer patient in the 21 st century: a new age, Semin. Oncol. 2004;31:11-15
2. Nusse R, Varmus HE, Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome, Cell 1982;31:99-109.
3. Pennisi E. How a growth control path takes a wrong turn to cancer? Science, 1998, 281: 1438-1439,1441.
4. Dierick H and Bejsovec A. Cellular mechanisms of wingless/Wnt signal transduction.Curr Top Dev Biol.1999;43:153-190.
5. Bienz M,Clevers H, Linking colorectal cancer to Wnt signaling, Cell 2000;103:311-320.
6. Polakis P, Wnt signaling and cancer, Genes Dev. 2000; 14:1837-1851.
7. Morin PJ, Sparks AB, Korinek V, et al.. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC, Science 199;275:1787-1790.
8. Korinek V, Barker N, Morin PJ, et al.. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APCK/Kcolon carcinoma, Science 1997;275:1784-1787.
9. Rhee CS, Sen M, Lu D, et aLWnt and frizzled receptors as potential targets for immuno-therapy in head and neck squamous cell carcinomas, Oncogene 2002;21:6598-6605.
10. Weeraratna AT, Jiang Y, Hostetter G,et al.. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma, Cancer Cell.2002;1:279-288.
11. Lu D, Zhao Y, Tawatao R,et al..Activation of the Wnt signaling pathway in chronic lymphocytic leukemia, Proc. Natl Acad. Sci. USA. 2004;101:3118—3123.
12. Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. Annual Reviews in Cell and Development Biology, 1998, 14: 59-88.
13. Gumbiner BM.. Propagation and localization of Wnt signaling. Curr Opin Genet Devel, 1998. 8: 430-435
14. Peifer M, Polakis P: Wnt signaling in onceogenesis and embryogenesis-a look outside the nucleus. Science 2000. 287: 1606-1609.
15. Kuhl M, Sheklahl LC, Park M, et al. The Wnt/Ca2~+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet 2000, 16: 279-283.
16. Peifer M, McEwen DG: The ballet of morphogenesis: unveiling the hidden choreographers. Cell 2002, 109: 271-274.
17. Capdevila J, Belmonte JCI: Extracellular modulation of the Hedgehog, Wnt and TGF-βsignaling pathways during embryonic development. Curr Opin Genet Dev 1999, 9: 427-433.
18. Saneyoshi T, Kume S, Amasaki Y, et al. The Wnt/calcium pathway activeates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature 2002, 417: 295-299.
19. Malbon CC, Wang H, Moon RT: Wnt signallyng and hetertrimeric G-Proteins: strange bedfellows or a classic romance? Biochem Biophys Res commun 2001, 287: 589-593.
20. Kuhi M, Geis K, Sheldahl LC, et al. Antagonistic regulation of convergent extension movements in Xenopus by Wnt/beta-catenin and Wnt/Ca~(2+) signaling. Mech Dev 2001, 106: 61-76.
21. Winktbauer R, Medina A, Swain RK, et al. Frizzled-7 signaling controls tissue separation during Xenopus. Nature 2001, 413: 856-860.
22. Sokol S: Arole for Wnts in morphogenesis and tissue polarity. Nat Cell Biol 2000, 2: E124-E125.
23. Akiyama T., Wnt/beta-catenin signaling, Cytokine Growth Factor Rev. 2000.11: 273-282.
24. Korinek V, Barker N, Moerer P, et al.. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4, Nat.Genet. 1998; 19:379-383.
25. Brennan KR, Brown AM, Wnt proteins in mammary development and cancer, J. Mammary Gland Biol. Neoplasia 2004;9:119-131.
26. Pandur P, Lasche M, Eisenberg LM,Kuhl M. Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis, Nature ,2002;418:636-641.
27. Reya T, Duncan AW, Ailles L, et al.. A role for Wnt signalling in self-renewal of haematopoietic stem cells, Nature 2003;423:409-414.
28. Rijsewijk F, Schuermann M, Wagenaar K,et al.. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless, Cell 1987;50:649-657.
29. Morrisey KK, Wnt signaling and pulmonary fibrosis, Am.J. Pathol. 2003;162:1393-1397.
30. Yamaguchi TP, Bradley A, McMahon AP,et al. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo, Development 1999:126:1211-1223.
31. Weidenfeld J, Shu W, Zhang L, et al. The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium, J. Biol. Chem. 2002;277:21061-21070.
32. Li C, Xiao J, Hormi K,et al.. Wnt5a participates in distal lung morphogenesis, Dev. Biol. 2002; 248:68-81.
33. Shu W, Jiang YQ, Lu MM, et al..Wnt7b regulates mesenchymal proliferation and vascular develop- ment in the lung, Development 2002;129:4831-4842.
34. Bonner AE, Lemon WJ, You M, Gene expression signatures identify novel regulatory pathways during murine lung development: implications for lung tumorigenesis, J. Med. Genet. 2003;40:408-417.
35. Chilosi M, Poletti V, Zamo A, et al..Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis, Am. J. Pathol.2003; 162:1495-1502.
36. Keith WN. From stem cells to cancer: balancing immortality and neoplasia, Oncogene 23 (2004) 5092-5094.
37. Reya T, Duncan AW, Ailles L, et al., A role for Wnt signalling in self-renewal of haematopoietic stem cells, Nature 423 (2003) 409-414.
38. Sato N, Meijer L, Skaltsounis L.et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor, Nat. Med. 10 (2004) 55-63.
39. Ross S E , Hemati N , Longo KA , et al . Inhibition of adipogenesis by Wnt signaling. Science , 2000 , 289 (5481): 950—953
40. Reya T, OpRiordan M, Okamura R , et al . Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism.lmmunity , 2000 , 13 (1): 15-24
41. Chenn A , Walsh C A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science , 2002 , 297 (5580): 365-369
42. Chenn A , Walsh C A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science , 2002 , 297 (5580): 365-369
43. Jamieson CH, Ailles LE,.Dylla SJ,, et al., Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML, N. Engl. J. Med. 2004,351:657-667.
44. Korinek V, Barker N, Moerer P, et al., Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4, Nat.Genet. 1998,19:379-383.
45. Gat U. DasGupta R, Degenstein L,et al. De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin, Cell. 1998; 95:605-614.
46. van de Wetering M, Sancho,E, Verweij C, et al., The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells, Cell 2002; 111:241-250.
47. Fuchs E and Segre JA.Stem cells: a new lease on life.Cell.2000; 100(1): 143-55.
48. Bienz M,Clevers H. Linking colorectal cancer to Wnt signaling .Cell ,2000,103 :3112320.
49. Reya T, Morrison SJ, Clarke MF, et al.Stem cells, cancer, and cancer stem cells, ature. 2001; 414(6859): 105-11.
50. Zhu AJ,Watt EM.β-catenin signaling modulates proliferative potential of human epidermal keratino- cytes independently of intercellular adhesion Development , 1999 , 126 :2258-2298.
51. Willert J ,Epping M,Pollack JR , et al . A transcriptional response to Wnt protein in human embryonic cancinoma cells.BMC Dev Biol ,2002 ,2(1):8-15.
52. Nusse R,Varmus HK, Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome, Cell 1982;31:99-109.
53. Katoh M, Expression and regulation of WNT1 in human ancer: up-regulation of WNT1 by beta-estradiol in MCF-7cells, Int. J. Oncol. 2003;22:209-212.
54. Wong SC, Lo SF, Lee KC,et al. Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours, J. Pathol.2002;196:145-153.
55. Chen S, Guttridge DC, You Z,et al.. Wnt-1 signaling inhibits apoptosis by activating beta-catenin/T cell factor-mediated transcription, J. Cell Biol. 2001; 152:87-96
56. He B, You L,Uematsu K,et al., A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells, Neoplasia 2004;6:7-14.
57. Katoh M, Frequent up-regulation of WNT2 in primary gastric cancer and colorectal cancer, Int. J. Oncol. 2001; 19:1003-1007.
58. Yoshida MC, Wada M, Satoh H, et al.. Human HST1 (HSTF1) gene maps to chromosome band 11q13 and coamplifies with the INT2 gene in human cancer, Proc. Natl Acad. Sci. USA 1988:85:4861-4864.
59. Roelink H, Wagenaar E, Nusse R, Amplification and proviral activation of several Wnt genes during progression and clonal variation of mouse mammary tumors, Oncogene 1992:7:487-492.
60. Nessling M, Solinas-Toldo S, Wilgenbus KK,et al.. Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN,MET, WNT2, and ERBB2, Genes Chromosomes Cancer 1998;23:307-316.
61. Katoh M, Kirikoshi H, Terasaki H,et al. WNT2B2 mRNA, up-regulated in primary gastric cancer, is a positive regulator of the WNT-beta-catenin-TCF signaling pathway, Biochem. Biophys. Res. Commun. 2001;289:1093-1098.
62. Vider BZ, Zimber A, Chastre K, et al.. Evidence for the involvement of the Wnt 2 gene in human colorectal cancer, Oncogene 1996;12:153—158.
63. Holcombe RP, Marsh JL,Waterman ML,et al..Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma, Mol. Pathol.2002;55:220-226.
64. Katoh M, Differential regulation of WNT2 and WNT2B amonghuman cancer, Int. J. Mol. Med. 2001 ;8:657-660.
65. Pham K, Milovanovic T, Barr RJ, et al.. Wnt ligand amongmalignant melanoma: pilot study indicating correlation with histopathological features, Mol. Pathol. 56 (2003) 280-285.
66. You L. He B, Xu Z.et al.. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells,Oncogene 2004;23:6170-6174.
67. Calvo R, West J, Franklin W,et al., Altered HOX and WNT7A amonghuman lung cancer, Proc. Natl Acad. Sci. USA 2000;97:12776-12781.
68. Ohira T, Gemmill RM, Ferguson K,et al.. WNT7a induces E-cadherin in lung cancer cells, Proc. Natl Acad. Sci. USA 2003; 100:10429-10434.
69. Kengaku M, Capdevila J, Rodriguez-Esteban C,et al.. Distinct WNT pathways regulating AER formation and dorsoventral polarity in the chick limb bud, Science 1998;298:1274-1277.
70 . Moon RT, Brown JD, Torres M, WNTs modulate cell fate and behavior during vertebrate development,Trends Genet. 1997; 13:157-162.
71. Saitoh T, Mine T, Katoh M, Frequent up-regulation of WNT5A mRNA in primary gastric cancer, Int. J. Mol. Med. 2002;9:515-519.
72. Weeraratna AT, Jiang Y, Hostetter G, et al.. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma, Cancer Cell 2002 1:279-288.
73. Liang H, Chen Q, Coles AH, et al.. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue, Cancer Cell 2003;4 349-360.
74. Nakano T, Tani M, Ishibashi Y, et al.. Biological properties and gene expression associated with metastatic potential of human osteosarcoma, Clin. Exp. Metastasis 2003;20:665-674.
75. Zeng L, Fagotto F, Zhang T, et al., The mouse fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation, Cell 1997;90:181—192.
76. Ponting CP, Phillips C, Davies KE, PDZ domains: targeting signalling molecules to sub-membranous sites, Bioessays 1997; 19:469-479.
77. Ponting CP, Bork P, Pleckstrin's repeat performance: a novel domain in G-protein signaling?, Trends Biochem. Sci. 1996;21:245-246.
78. Uematsu K, He B, You L,et al.. Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression, Oncogene 2003;22:7218—7221.
79. Uematsu K, Kanazawa S, You L, et al.Wnt pathway activation in mesothelioma: evidence of dishevelled overexpression and transcriptional activity of beta-catenin, Cancer Res. 2003:63:4547-4551.
80. Wharton Jr. KA. Runnin' with the Dvl: proteins that associate with Dsh/Dvl and their significance to Wnt signal transduction, Dev. Biol. 2003;253:l—17.
81. Hommura F, Furuuchi K, Yamazaki K,et al.. Increased expression of beta-catenin predicts better prognosis in nonsmall cell lung carcinomas, Cancer 2002;94:752-758.
82. Retera JM, Leers MP, Sulzer MA,et al. The expression of beta-catenin in non-small-cell lung cancer: a clinicopathological study, J. Clin. Pathol. 1998;51: 891-894.
83. Kase S, Sugio K, Yamazaki K, et al.. Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance.Clin. Cancer Res. 2000;6:4789-4796
84. Shigemitsu K, Sekido Y, Usami N,et al.. Genetic alteration of the beta-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion, Oncogene 2001;20:4249-4257.
85. Nakatani Y, Masudo K, Miyagi Y.et al.. Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules, Mod. Pathol. 2002;15:617-624.
86. Cooper CA, Bubb VJ, Smithson N,et al.. Loss of heterozygosity at 5q21 in non-small cell lung cancer: a frequent event but without evidence of apc mutation, J. Pathol. 1996;180:33—37.
87. Horii A, Nakatsuru S, Miyoshi Y,et al.. Frequent somatic mutations of the APC gene In human pancreatic cancer, Cancer Res. 1992;52:6696-6698.
88. Furuuchi K, Tada M, Yamada H,et al..Somatic mutations of the APC gene in primary breast cancers, Am. J. Pathol. 2000; 156:1997-2005
89 . Ohgaki H, Kros JM, Okamoto Y,et al.. APC mutations are infrequent but present in human lung cancer, Cancer Lett. 2004;207:197-203.
90. Veeman MT,Axelrod JD, Moon RT, A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling, Dev. Cell 2003;5:367-377.
91. Habas R, Kato Y, He X, Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daaml, Cell 2001 ;107: 843-854.
92. Choi SC, Han JK, Xenopus Cdc42 regulates convergent extension movements during gastrulation through Wnt/Ca2C signaling pathway, Dev. Biol. 2002;244:342-357.
93. Penzo-Mendez A, Umbhauer M, Djiane A,et al.. Activation of Gbetagamma signaling downstream of Wnt-11/Xfz7 regulates Cdc42 activity during Xenopus gastrulation, Dev. Biol. 2003; 257:302-314.
94. Hordijk PL, ten Klooster JP, van der Kammen RA,et al..Inhibition of invasion of epithelial cells by Tiam1-Rac signaling, Science 1997;278:1464-1466.
95 . Soon LL, Yie TA, Shvarts A,et al.. Overexpression of WISP-1 downregulated motility and invasion of lung cancer cells through inhibition of Rac activation, J. Biol. Chem. 2003;278:11465-11470.
96 . Tao W, Pennica D, Xu L, et al.. Wrchl, a novel member of the Rho gene family that is regulated by Wnt-1, Genes Dev. 2001; 15:1796-1807.
97. Habas R, Dawid IB, He X, Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation, Genes Dev. 2003; 17:295-309.
98. Allal C, Favre G, Couderc B, et al.. RhoA prenylation is required for promotion of cell growth and transformation and cytoskeleton organization but not for induction of serum response element transcription, J. Biol. Chem. 2000;275:31001-31008.
99. Mazieres J, Antonia T, Daste G, et al.. Loss of RhoB amonghuman lung cancer progression, Clin. Cancer Res. 2004; 10:2742-2750.
100. Ikoma T, Takahashi T, Nagano S,et al.. A definitive role of RhoC in metastasis of orthotopic lung cancer in mice, Clin. Cancer Res. 2004;10:1192-1200.
101. del Peso L, Hernandez-Alcoceba R, Embade N,et al. Rho proteins induce metastatic properties in vivo, Oncogene 1997; 15:3047-3057.
102. Yao R, Wang Y, Lubet RA,et al.. Differentially expressed genes associated with mouse lung tumor progression, Oncogene 2002;21:5814-5821.
103. Malliri A, Collard JR, Role of Rho-family proteins in cell adhesion and cancer, Curr. Opin. Cell Biol. 2003;15:583-589.
104. Boutros M, Paricio N, Strutt DI,et al.. Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling, Cell 1998;94:109-l 18.
105. Moriguchi T, Kawachi K, Kamakura S,et al.. Distinct domains of mouse dishevelled are responsible for the c-Jun N-terminal kinase/stress-activated protein kinase activation and the axis formation in vertebrates, J. Biol. Chem. 1999;274:30957-30962.
106. You L, He B, Uematsu K, et al..Inhibition of Wnt-1 signaling induces apoptosis in betacatenin-deficient mesothelioma cells, Cancer Res. 2004;64:3474-3478.
107. Kawano Y, Kypta R, Secreted antagonists of the Wnt signalling pathway, J. Cell Sci. 2003; 116:2627-2634.
108. Ko J. Ryu KS, Lee YH,et al.. Human secreted frizzled-related protein is downregulated and induces apoptosis in human cervical cancer, Exp. Cell Res. 2002;280:280-287
109. Ugolini F, Charafe-Jauffret E, Bardou VJ, et al.. WNT pathway and mammary carcinogenesis: loss of expression of candidate tumor suppressor gene SFRPl in most invasive carcinomas except of the medullary type, Oncogene. 2001 ;20:5810-5817.
110. To KF, Chan MW, Leung WK,et al.. Alterations of frizzled (Fz3) and secreted frizzled related protein (hsFRP) amonggastric cancer, Life Sci. 2001 ;70:483-489.
111. Suzuki H, Gabrielson K,Chen W, et al.. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer, Nat. Genet. 2002;31:141-149.
112. Suzuki H, Watkins DN, Jair KW, et al.. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet. 2004 ;36(4):417-22..
113. Caldwell GM, Jones C, Gensberg K, et al. The Wnt antagonist sFRPl in colorectal tumorigenesis, Cancer Res. 2004;64:883-888.
114. Hsieh JC, Kodjabachian L, Rebbert ML, et al.. A new secreted protein that binds to Wnt proteins and inhibits their activities, Nature 1999;398:431-436.
115. Wissmann C, Wild PJ, Kaiser S, et al.. WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer, J. Pathol. 2003;201:204-212.
116. Mazieres J, He B, You L, et al..Wnt inhibitory factor-1 is silenced by promoter hyperme-thylation in human lung cancer, Cancer Res. 2004;64:4717-4720.
117. Wong SC, Lo SF, Lee KC,et aL.Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours, J. Pathol. 2002; 196:145-153.
118. Lee AY, He B, You L,et aL.Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma, Oncogene 2004; 23(39): 6672-6676
119. Fedi P, Bafico P, Nieto Soria A, et al.. Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling, J. Biol. Chem. 1999; 274: 19465-19472.
120. Tsuji T, Miyazaki M, Sakaguchi M, et al. A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines, Biochem. Biophys. Res. Commun. 2000; 268: 20-24.
121. Nozaki I, Tsuji T, Iijima C, et al.. Reduced expression of REIC/Dkk-3 gene in non-small cell lung cancer, Int. J. Oncol. 2001; 19: 117-121
122. Tsuji T, Nozaki I, Miyazaki M, et al.. Antiproliferative activity of REIC/Dkk-3 and its significant down-regulation in non-small-cell lung carcinomas, Biochem. Biophys. Res. Commun. 2001; 289: 257-263.
123. Kobayashi K, Ouchida M, Tsuji T, et al.. Reduced expression of the REIC/Dkk-3 gene by promoter-hypermethylation in human tumor cells, Gene 282 (2002) 151-158.
2. Mulshine JL, Treston AM, Brown PH, et al. Initiators and promoters of lung cancer. Chest, Jan 1993; 103(1 Suppl): 4S-11S.
3．周清华，孙燕主编．肺癌新理论新技术进展．四川大学出版社，2003年12月第1版，90-110
4. Steeg PS, Bevilacqua G, Kopper L, et al. Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst. 1988; 80(3): 200-204.
5. Steeg PS, Cohn KHand Leone A. Tumor metastasis and nm23: current concepts. Cancer Cells. Jul 1991; 3(7): 257-62
6．周清华，陈军，刘伦旭，等．nm23-H1基因缺失与人非小细胞肺癌转移相关性研究，中国胸心血管外科临床杂志，1998：5(3)：131-134
7．周清华，车国卫，覃杨，等．nm23-H1逆转肺癌转移表型及其分子机制实验研究．中国肺癌杂志．2003．6(2)：141-143
8．周清华，王艳萍，车国卫，等．人大细胞肺癌细胞系NL9980和L9981的建立及其生物学特性研究．中国肺癌杂志，2003，6(6)：464-468
9．付军科，周清华，朱文，等．nm23-H1基因能上调人肺癌细胞株L9981中GSK-3β激酶活性．中国肺癌杂志，2004，7(2)：89-94．
10. Ali A. Hoeflich KP, and Woodgett JR. Glycogen synthase kinase-3: properties, functions, and regulation. Chem. Rev, 2001, 101, 2527-2540.
11. de la Rosa A, Williams RL, Steeg PS.nm23/nucleoside diphosphate kinase: toward a structural and biochemical understanding of its biological functions.Bioessays. 1995 Jan;17(1):53-62.
12. Paul D. Wagner, Ngoc-Diep Vu. Phosphorylation of ATP-Citrate Lyase by Nucleoside Diphosphate Kinase. 1995;270:21758-21764
13. Jose M.P. Freije, Pilar Blay, et al. Site-directed Mutation of m23-H1. 1997; 272: 5525-5532
14. Engel M, Veron M, Theisinger B,et al. A novel serine/threonine-specific protein phosphor-transferase activity of nm23/nucleoside-diphosphate kinase. Eur. J. Biochem, 234:200-207
15. Nicholas J. MacDonald, Jose M. et al. Site-directed Mutagenesis of nm23-H 1. J.Biol.Chem. 1996; 271: 25107-25116
16. Huelsken J,Behrens J. The Wnt signaling pathway. J Cell Science 2002,115, 3977-3978
17. Biggs J, Hersperger E, Steeg PS, 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
18. Polakis P. Wnt signaling and cancer. Genes Dev 2000; 14: 1837-1851.
19. He X., Saint-Jeannet JP, Wang, Y, et al. A member of the Frizzled protein family mediating axis induction by Wnt-5A. Science 1997.275: 1652-1654.
20. Lee, F.S., Lane, T.F., Kuo, A., et al. Insertional mutagenesis identifies a member of the Wnt gene family as a candidate oncogene in the mammary epithelium of int-2/Fgf-3 transgeneic mice. Proc. Natl. Acad. Sci. 1995, 92: 2268-2272.
21. Nusse, R. and Varmus, H.E. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 1982.31: 99-109.
22. Roelink, H., Wagenaar, E., Lopes da Silva, S., et al. Wnt-3, a gene activated by proviral insertion in mouse mammary tumors, is homologous to int-1/Wnt-1 and is normally expressed in mouse embryos and adult brain. Proc.Natl. Acad. Sci. 1990.87: 4519-4523.
23. Cui J. Zhou X, Liu Y K,et al. Wnt signaling in hepatocellular carcinoma: Analysis of mutation and expression of beta-catenin, T-cell factor-4 and glycogen synthase kinase 3-beta genes. J Gastroenterol. Hepatol. 2003; 18:280-287.
24. Clements W M, Wang J, Sarnaik A, et al. p-catenin mutation is a frequent cause of Wnt Pathway activation in gastric cancer. Cancer Res,2002,62:3503-3506.
25. Hommura F, Furuuchi K, Yamazaki K, et al. Increased expression of p-catenin predicts better prognosis in non small cell lung carcinomas. Cancer,2002,94(3):752-758
26. Li L. Yuan H., Xie W, et al. Dishevelled proteins lead to two signaling pathways. Regulation of LEF-1 and c-Jun N-terminal kinase in mammalian cells. J. Biol. Chem. 1999b.274:129-134.
27. Seldin DC. and Leder P. Casein kinase II alpha transgenee-induced murine lymphoma: Relation to theileriosis in cattle. Science 1995.267: 894-897.
28. Song DH, Sussman DJ, and Seldin DC. Endogenous protein kinase CK2 (casein kinase II) participates in Wnt signaling in mammary epithelial cells. J. Biol. Chem. 2000. 275: 23790 - 23797
29. Willet K, Brink M, Woodard A. Casein kinase 2 associates with and phosphorylates dishevelled. EMBO J. 1997.16: 3089-3096.
30. Uematsu K, He Biao, You Liang, et al. Activation of the Wnt pathway in non small cell lung cancer: evidence of disheveled overexpression. Oncogene, 2003;22:7218-7221.
31. Dommguez I, Itoh K., and Sokol SY. Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos. Proc. Natl. Acad. Sci. 1995,92: 8498-8502.
32. He X. Saint-Jeannet JP, Woodgett JR., et al. Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos. Nature 1995.374: 617-623.
33. Hedgepeth CM, Deardorff MA, Rankin K, et al. Regulation of glycogen synthase kinase 3 and downstream Wnt signaling by axin. Mol. Cell Biol. 1999b, 19: 7147-7157.
34. Ikeda S, Kishida S, Yamamoto H, et al. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3β and β-catenin and promotes GSK-3β dependent phosphorylation of β-catenin. EMBO J. 1998,17: 1371-1384.
35. Itoh K, Krupnik VE, and Sokol SY. Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and beta-catenin. Curr. Biol. 1998,8: 591-594.
36. Li, L., Yuan, H., Weaver, C.D., et al. Axin and Fratl interact with dvl and GSK, bridging Dvl to GSK in Wnt- mediated regulation of LEF-1. EMBO J. 1999a,18: 4233-1240.
37. Nakamura, T., Hamada, F., Ishidate, T., et al. . Axin, an inhibitor of the Wnt signaling pathway, interacts with beta- catenin, GSK-3beta and APC and reduces the beta-catenin level. Genes Cells 1998a,3: 395-403.
38. Rubinfeld B, Albert 1, Porfiri E, et al. Binding of GSK3aβ to the APC-β-catenin complex and regulation of complex assembly. Science 1996,272: 1023-1026.
39. Yamamoto H, Kishida S, Kishida M, et al. Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3β regulates its stability. J. Biol. Chem. 1999,274: 10681-10684.
40. Thomas GM, Frame S, Goedert M, et al. A GSK3β-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett. 1999.458:247-251.
41. Salic A, Lee E, Mayer L, et al. Control of beta-catenin stability: Reconstitution of the cytoplasmic steps of the Wnt pathway in Xenopus egg extracts. Mol. Cell: 2000, 5: 523-532.
42. Rubinfeld B., Albert I., Porfiri E., et al. Binding of GSK3 to the APC—Catenin Complex and Regulation of Complex Assembly. Science, 1996; 272: 1023-1026.
43. Hart MJ, de los Santos R., Albert IN, et al. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol, 1998; 8(10): 573-581.
44. Ikeda S, Kishida M, Matsuura Y, et al. GSK-3 beta-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by beta-catenin and protein phosphatase 2A complexed with Axin. Oncogene, 2000; 19(4): 537-545.
45. Hart MJ, de los Santos R, Albert, et al. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr. Biol. 1998. 8: 573-581.
46. Ikeda. S., Kishida, S., Yamamoto, H., et al.. Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3βand β-catenin and promotes GSK-3β-dependent phosphorylation of β-catenin. EMBO J. 1998, 17: 1371-1384.
47. Satoh S, Daigo Y, Furukawa Y, et al. AXIN1 mutations in hepatocellular carcinomas, and growth suppression in cancer cells by virus-mediated transfer of AXIN1. Nat. Genet. 2000; 24: 245-250.
48. Kawasaki Y, Sato R, Akiyama T. Mutated APC and Asef are involved in the migration of colorectal tumor cells. Nat Cell Biol, 2003, 5(3): 211-215.
49. Muller T, Bain G, Wang X, et al. Regulation of epithelial cell migration and tumor formation by β-catenin signaling. Exp Cell Res, 2002, 280(1)119-133.
50. Dempke W, Rie C, Grothey A, et al. Cyclooxygenase-2: a novel target for cancer chemotherapy. J Cancer Res Clin Oncol,2001,127(7):411-417.
51. Kenneth JL and Thomas DS.Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2~(-ΔΔCr) Method.METHODS.2001;25:402-408
52. Leone A, Flatow U, Uing CR., et al. Recuced tumor incidence metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell, 1991, 65 (1): 25-35
53. Kantor JD, Mccormick B, Steeg PS, et al. Inhibition of cell mortality after nm23 transfection of human and marine tumor. Cancer Res. 1993; 53(8): 1971-1973
54. Lacombe ML, Milon L, Munier A, et al. The human nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr. 2000;32(3):247-258.
55. Otero AS. nm23/nucleoside diphosphate kinase and signal transduction. J Bioenerg Biomembr 2000; 32:269-275
56. Hartsough MT, Steeg PS nm23/nucleoside diphosphate kinase in human cancers. J Bioenerg Biomembr 2000;32:301-308
57. Kimura N, Shimada N, Fukuda M, et al. Regulation of cellular functions by nucleoside diphosphate kinases in mammals. J Bioenerg Biomembr 2000;32:309-315
58. Postel EH, Berberich SJ, Rooney JW, et al. Human nm23/nucleoside diphosphate kinase regulates gene expression through DNA binding to nuclease-hypersensitive transcriptional elements. J Bioenerg Biomembr 2000;32:277-284
59. Lacombe ML, Milon L, Munier A, et al. The human nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr 2000;32:247-258
60. Postel EH. Multiple biochemical activities of nm23/NDP kinase in gene regulation. J Bioenerg Biomembr, 2003; 35(1):31-40
61. Lombardi D, Mileo AM. Protein interactions provide new insight into nm23/nucleoside diphosphate kinase functions. J Bioenerg Biomembr, 2003; 35(1)67-71.
62. Kraeft SK, Traincart F, Mesnildrey S, et al.. Nuclear localization of nucleoside diphosphate kinase type B (nm23-H2)in cultured cells, Exp. Cell Res. 1996; 227: 63-69
63. 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,
64. Lascu I, Gonin P. The catalytic mechanism of nucleoside diphosphate kinase. J Bioenerg Biomembr, 2000, 32(3): 237-246.
65. Godfried MB, Veenstra M, Vsluis P, et al. The N-myc and c-myc downstream pathways include the chromosome 17q genes nm23-H_1 and nm23-H_2. Oncogene, 2002; 21(13): 2097-2101.
66. Hayer J, Engel M, Seifert M, et al. Overexpression of nm23-H_4 RNA in colorectal and renal tumors. Anticancer Res., 2001; 21(4A): 2821-2825.
67. Munier A, Serres C, Kann ML, et al. nm23/NDP kinases in human male gene cells: role in sperminogenesis and sperm motility? Exp Cell Res. 2003; 289(2): 295-306.
68. Dooley S, Seib T, Engel M, et al. Isolation and characterization of the human genomic locus coding for the putative metastasis control gene nm23-H1. Hum Genet 1994; 93(1): 63-66.
69．骆成玉，祝学光．nm23基因的研究近况及其临床应用前景．国外医学外科学分册，1995；22(1)：24
70. Leone A, Flatow U, VanHoutte K et al. 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 1993; 8: 2325-2333.
71. Bhujwalla Z, Aboagye E, Gilles R et al. nm23-transfected MDAMB-435 human breast carcinoma cells form tumors with altered phospholipid metabolism and pH: A 31P nuclear magnetic resonance study in vivo and in vitro. Magn Res Med 1999; 41: 897-903.
72. Russell R, Pedersen A, Kantor J et al. Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines. Br J Cancer 1998; 78: 710-717.
73. Fukuda M, Ishii A, Yasutomo Y et al. Metastatic potential of rat mammary adenocarcinoma cells associated with decreased expression of nucleoside diphosphate kinase/nm23: Reduction by transfection of NDP Kinase a isoform, an nm23-H2 gene homolog. Int J Cancer 1996; 65: 531-537.
74. Leone A, Flatow U, King CR et al. Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell 1991; 65: 25-35.
75. Baba H, Urano T, Okada K et al. 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 1995; 55: 1977-1981.
76. Parhar RS, Shi Y, Zou M et al. Effects of cytokine mediated modulation of nm23 expression on the invasion and metastatic behavior of B16F10 melanoma cells. Int J Cancer 1995; 60: 204-210.
77. Miele ME, Rosa ADL, Lee JH et al. Suppression of human melanoma metastasis following introduction of chromosome 6 is independent of NMEl (nm23). Clin Exp Metastasis 1997; 15:259-265.
78. Tagashira H, Hamazaki K, Tanaka N et al. Reduced metastatic potential and c-myc overexpression of colon adenocarcinoma cells (Colon 26 line) transfected with nm23-R2 rat nucleoside diphosphate kinase an isoform. Int J Mol Med 1998; 2: 65-68.
79. Miyazaki H, Fukuda M, Ishijima Y et al. Overexpression of nm23-H2/NDP Kinase B in a human oral squamous cell carcinoma cell line results in reduced metastasis, differentiated phenotype in the metastatic site, and growth factor-independent proliferative activity in culture. Clin Cancer Res 1999; 5: 4301-4307.
80. Lombardi D, Lacombe ML, and Paggi MG.nm23: unraveling its biological function in cell differentiation. J Cell Physiol. 2000; 182(2): 144-149.
81. 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(1):53-62.
82. Hartsough MT, Steeg PS.nm23/nucleoside diphosphate kinase in human cancers. J Bio-energ Biomembr. 2000;32(3):301-308.
83. Otero AS.nm23/nucleoside diphosphate kinase and signal transduction. J Bioenerg Biomembr. 2000;32(3):269-275.
84. Leone A, Flatow LI, King CR, et al. Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell. 1991;65(1):25-35.
85. Baba, H Urano T, Okada, K et al. Two isotypes of murine nm23/nucleoside diphosphate kinase, nm23-Ml and nm23-M2, are involved in metastatic suppression of a murine melanoma line. Cancer Research, 1995;55:1977-1981
86. Barnes R, Masood S, Barker E, et al. Low nm23 protein amonginfiltrating ductal breast carcinomas correlates with reduced patient survival. American J Pathology, 1991, 139: 245-250
87. Florenes VA, Aamdal S, Myklebost O, et al. Levels of nm23 messenger RNA in metastatic malignant melanomas: inverse correlation to disease progression. Cancer Res., 1992; 52:6088-6091.
88. Yamaguchi A, Urano T, Goi T, et al.. Expression of human nm23-H1 and nm23-H2 proteins in hepatocellular carcinoma.Cancer, 1994;73(9):2280-2284.
89. Nakayama T, Ohtsuru A, Nakao K, et al. Amonghuman hepatocellular carcinoma of nucleoside diphosphate kinase, a homologue of the nm23 gene product. J Natl Cancer Inst. 1992; 84(17):1349-I354.
90. Nakayama H, Yaqui W, Yokosuka H, et al. Reduced expression of nm23 is associated with metastasis of human gastric carcinomas. Jpn J Cancer Res. 1993; 84(2): 184-190.
91. Bertheau P, De La rosa A. Steeg PS, et al. nm23 protein in neoplasmtic and nonneoplasmtic thyroid tissues. Am J Patol, 1994; 145:26-32
92. Igawa M, Rukstalis DB, Tanabe T, et al. High levels of nm23 expression is related to cell proliferation in human prostate cancer.Cancer Res., Mar 1994; 54: 1313-1318.
93. Zou M, Shi Y,al-Sedairy S, et al. High levels of nm23 gene amongadvanced stage of thyroid carcinomas.Br J Cancer, 1993; 68(2): 385-288.
94. Kawakubo Y, Sato Y, Koh T, et al. Expression of nm23 protein in pulmonary adeno-carcinomas: inverse correlation to tumor progression. Lung Cancer, 1997:17(1): 103-113.
95. Engel M, Theisinger B, Seitz G, et al. High levels of nm23-H1 and nm23-H2 messenger RNA in human squamous cell lung carcinoma are associated with poor differentiation and advanced tumor stages. Int J Cancer, 1993,55(3):375-379
96. Ozeki Y, Takishima K, and Mamiya G Immunohistochemical analysis of nm23/NDP kinase amonghuman lung adenocarcinoma: association with tumor progression in Clara cell type. Jpn J Cancer Res, 1994; 85(8): 840-846.
97. Bertheau P, De La Rosa A, Steeg PS. et al. nm23 protein in neoplastic and non-neoplastic thyroid tissues. Am J Patol, 1994;145(1): 26-32.
98. Engel M, Theisinger B, Seib T,et al. High levels of nm23-H1 and nm23-H2 messenger RNA in human squamous-cell lung carcinoma are associated with poor differentiation and advanced tumor stages. Int J Cancer, 1993; 55(3): 375-379.
99. Volm M, Martern J, Koomagi R. Association between nm23-H_1 expression. Proliferation and apoptosis in non-small cell lung carcinoma. Clin Exp metastasis. 1998; 16(7): 596-602.
100．王海峰，陈晓峰，高文等．nm23mRNA表达与肺癌的分化转移及病理之间的相关性研究．中国临床医学，2004；11(2)：24-27
101. Huwer H, Engel M, Welter C, et al. Squamous cell carcinoma of the lung: does the nm23 gene expression correlate to the tumor stage? Thorac Cardiovasc Surg, 1994; 42(5): 298-301.
102．陈军，周清华，覃杨，等．人肺癌中nm23等位基因缺失的研究．中国肺癌杂志．2000；3(1)：8-13．
103. Lai Ww, Wu MH, Yan JJ, et al. Immunohistochemical analysis of nm23-H_1 in stage Ⅰ non-small cancer: a useful marker in prediction of metastases. Ann Thorac Surg. 1996. 62(5): 1500-1504.
104．陈琼．陈全群，李国虎．原发性肺癌nm23基因mRNA表达的研究．中国现代医学杂志．2001；11(4)：18-121
105. Ozeki Y. Takishima K, Mamiya G, et al. Immunohistochemical analysis of nm23/NDP kinase amonghuman lung adenocarcinoma: Association with tumor progression in clara cell type. Jpn J Cancer Res. 1994. 85(8): 840-845
106. Higashiyama M, Doi O, Yokouchi H., et al.. Immuunohistochemical analysis of nm23 gene product/NDP kinase amongpulmonary adenocarcinoma: Lack of prongnostic value. Br J Cancer. 1992, 63(2): 533.
107．陈晓峰，周清华，石应康．nm23与肺癌转移和预后关系的研究进展．中国胸心外科临床杂志．1997；4(2)：48-50
108．刘伦旭，覃扬，周清华，等．Northern印迹杂交分析nm23基因在人肺癌中的表达研究． 中华肿瘤杂志，1998，20(5)：342-344
109．雷文东，张汝刚，闫水忠，等．nm23基因在人肺癌中的表达及其与肺癌淋巴结转移的关系．中华肿瘤杂志，1994，16(4)：277-279
110. Kawakabo Y, Sato Y, Koh T, et al. Expression of nm23 protein in pulmonary adeno-carcinomas: inverse correlation to tumor progression. Lung Cancer, 1997, 17(1): 103-113.
111. Huwer H, Kalweit G, Engel M, et al. Expression of candidate tumor suppression gene nm23 in the bronchial system of patients with squamous cell lung cancer. European journal of cardio-thoracic surgery. 1997; 11 (2): 206-209
112. Wu WL, Ming HW, Jing JY, et al. Immunohistochemical Analysis of nm23-H1 in Stage Ⅰ Non-Small Cell Lung Cancer: A Useful Marker in Prediction of Metastases. Ann. Thorac. Surg., 1996; 62: 1500—1504.
113. Ohta Y, Nozaki Z, Nozawa H, et al. The predictive value of vascular endothelial growth factor and nm23 for the diagnosis of occult metastasis in non-small cell lung cancer. Jpn J Cancer Res, Mar 2001; 92(3): 361-6.
114. MacDonald NJ, De la Rosa A, Benedict MA, A serine phosphorylation of nm23, and not its nucleoside diphosphate kinase activity, correlates with suppression of tumor metastatic potential J. Biol. Chem., 1993; 268: 25780-25789.
115. Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. Annual Reviews in Cell and Development Biology, 1998, 14: 59-88.
116. Peifer M, Polakis P. Wnt signaling in onceogenesis and embryogenesis-a look outside the nucleus. Science 2000. 287: 1606-1609.
117. Kuhl M, Sheklahl LC, Park M, et al. The Wnt/Ca2~+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet 2000, 16: 279-283.
118. Peifer M, McEwen DG: The ballet of morphogenesis: unveiling the hidden choreographers. Cell 2002, 109:271-274.
119. Capdevila J, Belmonte JCI: Extracellular modulation of the Hedgehog, Wnt and TGF-β signaling pathways during embryonic development. Curr Opin Genet Dev 1999, 9:427-433.
120. Saneyoshi T, Kume S, Amasaki Y, et al. The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature 2002, 417:295-299.
121. Malbon CC, Wang H, Moon RT: Wnt signaling and hetertrimeric G-Proteins: strange bedfellows or a classic romance? Biochem Biophys Res commun 2001, 287:589-593.
122. Kuhi M, Geis K, Sheldahl LC, et al. Antagonistic regulation of convergent extension movements in Xenopus by Wnt/beta-catenin and Wnt/Ca~(2+) signaling. Mech Dev 2001, 106:61-76.
123. Winklbauer R, Medina A, Swain RK, et al. Frizzled-7 signaling controls tissue separation during Xenopus. Nature 2001,413:856-860.
124. Sokol S: Arole for Wnts in morphogenesis and tissue polarity. Nat Cell Biol 2000, 2:E124-E125.
125. Akiyama T., Wnt/beta-catenin signaling. Cytokine Growth Factor Rev. 2000.11: 273-282.
126. Tulac S, Nayak NR, Kao LC, et al. Identification, characterization, and regulation of the canonical Wnt signaling pathway in human endometrium. J Clin Endocrinol Metab, 2003, 88(8):3860 -3866.
127. Miller JR. Wnt signaling transduction .In: Alison M ed. The cancer handbook [M]. London: Nature Publushing Group, 2002:195 - 208.
128. Meirmanov S,NakashimaM, Rogounovitch T, et al. Small cell carcinoma of the endo-metrium: report of a case with analysis of Wnt/beta-catenin pathway. Pathol Res Pract, 2003, 199 (8): 551 -558.
129. Lustig B, Behrens J. The Wnt signaling pathway and its role in tumor development. Cancer Res Clin Oncol, 2003,129:199-221.
130. Kikuchi A. Tumor formation by genetic mutations in the components of the Wnt signaling pathway . Cancer Sci, 2003, 94(3): 225 - 229.
131. Clements WM, Lowy AM, Groden J. Adenomatous polyposis coli/beta-catenin interaction and downstream targets: altered gene amonggastrointestinal tumors.Clin Colorectal Cancer,2003, 3 (2): 113-120.
132. Li H, Pamukcu R, Thomp son WJ. beta2Catenin signaling: therapeutic strategies in oncology. Cancer Biol Ther, 2002,1(6):621-625.
133. Miao J, Kusafuka T, Okada A. Detection of a novel alteration of the Axin gene in various pediatric neoplasms. Oncol Rep, 2003, 10(6): 1943 -1946.
134. Wharton KA Jr. Runnin with the Dvl: proteins that associate with Dsh/Dvl and their significance to Wnt signal transduction .Dev Biol, 2003, 253 (1) : 1 - 17.
135. Peifer M, Polakis P. Wnt signaling in oncogenesis and embryo genesis/a look outside the nucleus. Science, 2000, 287: 1606 -9.
136. Waltzer L,BienzM. The control of beta - catenin and TCF during embryonic development and cancer. Cancer Metastasis Rev, 1999, 18: 231 - 246.
137. Kantor JD,McCormick B, Steeg PS, et al. Inhibition of cell mortility after nm23 transfection of human and murine tumor cells. Cancer Res, 1993; 53 (9):1971-1963.
138. Macdonald NJ ,DelaRosa A ,BenedictMA , et al. A serine phosphorylation of nm23 and not its nucleoside diphosphate kinase activity, correlatesw ith supp ression of tumor metastatic potential. J Biol Chem, 1993;268(34):25780- 25789.
139. Korinek V, Barker N, Moerer P, et al.. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4, Nat. Genet. 1998; 19: 379-383.
140. Brennan KR, Brown AM, Wnt proteins in mammary development and cancer, J. Mammary Gland Biol. Neoplasia 2004; 9: 119-131.
141. Pandur P, Lasche M, Eisenberg LM, Kuhl M. Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis, Nature, 2002; 418: 636-641.
142. Reya T, Duncan AW, Ailles L, et al.. A role for Wnt signalling in self-renewal of haematopoietic stem cells, Nature 2003; 423: 409-414.
143. Rijsewijk F, Schuermann M, Wagenaar K, et al.. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless, Cell 1987; 50: 649-657.
144. Morrisey KK, Wnt signaling and pulmonary fibrosis, Am. J. Pathol. 2003; 162: 1393-1397.
145. Yamaguchi TP, Bradley A, McMahon AP, et al. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo, Development 1999: 126: 1211-1223.
146. Weidenfeld J, Shu W, Zhang L, et al.. The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium, J. Biol. Chem. 2002; 277: 21061-21070.
147. Li C, Xiao J, Hormi K, et al.. Wnt5a participates in distal lung morphogenesis, Dev. Biol. 2002; 248: 68-81.
148. Shu W, Jiang YQ, Lu MM, et al.. Wnt7b regulates mesenchymal proliferation and vascular development in the lung, Development 2002; 129: 4831-4842.
149. Bonnet AE, Lemon WJ, You M, Gene expression signatures identify novel regulatory pathways during murine lung development: implications for lung tumorigenesis, J. Med. Genet, 2003; 40: 408-417.
150. Chilosi M, Poletti V, Zamo A, et al.. Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis, Am. J. Pathol. 2003; 162: 1495-1502.
151. Hommura F, Furuuchi K, Yamazaki K, et al.. Increased expression of beta-catenin predicts better prognosis in nonsmall cell lung carcinomas, Cancer 2002; 94: 752-758.
152. Retera JM, Leers MP, Sulzer MA, et al.. The expression of beta-catenin in non-small-cell lung cancer: a clinicopathoiogical study, J. Clin. Pathol. 1998; 51: 891-894.
153. Kase S, Sugio K, Yamazaki K, et al.. Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance, Clin. Cancer Res. 2000; 6: 4789-4796
154. Sunaga N, Kohno T, Kolligs FT, et al. Constitutive activation of the Wnt signaling pathway by CTNNB1 (beta-catenin) mutations in a subset of human lung adenocarcinoma. Genes Chromosomes Cancer, 2001; 30(3): 316-321.
155. Shigemitsu K, Sekido Y, Usami N, et al.. Genetic alteration of the beta-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion, Oncogene 2001; 20: 4249-4257.
156. Nakatani Y, Masudo K, Miyagi Y. et al.. Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules, Mod. Pathol. 2002; 15: 617-624.
157. Uematsu K, He Biao, You Liang, et al. Activation of the Wnt pathway in non small cell lung cancer: evidence of disheveled overexpression. Oncogene, 2003, 23: 7218-7221.
158. Hommura F, Furuuchi K, Yamazaki K, et al. Increased expression of β-catenin predicta better prognosis in non-small cell lung carcinomas. Cancer 2002; 94: 752-758
159．付军科，周清华，朱文，等．nm23-H_1基因转染对人高转移大细胞肺癌细胞株L9981中β-catenin表达的影响．中国肺癌杂志．2004；7(6)：471-474
160. Rosengard AM, Krutzsch HC, Shearn A,et al.Reduced nm23/Awd protein in tumour metastasis and aberrant Drosophila development.Nature, 1989; 342(6246): 177-180.
161. Keith WN. From stem cells to cancer: balancing immortality and neoplasia, Oncogene 23 (2004) 5092-5094.
162. T. Reya, A.W. Duncan, L. Allies, J. Domen. D.C. Scherer, K. Willert, et al., A role for Wnt signalling in self-renewal of haematopoietic stem cells, Nature 423 (2003) 409-414.
163. Sato N, Meijer L, Skaltsounis L,et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3 -specific inhibitor, Nat. Med. 10 (2004) 55-63.
164. Ross SE , Hemati N , Longo KA , et al . Inhibition of adipogenesis by Wnt signaling. Science , 2000 , 289 (5481): 950-953
165. Reya T, OpRiordan M, Okamura R, et al. Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism. Immunity , 2000 ,13(1): 15-24
166. Cherui A , Walsh C A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science , 2002 , 297 (5580): 365-369
167. Chenn A , Walsh C A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science , 2002 , 297 (5580): 365-369
168. Jamieson CH, Allies LE,.Dylla SJ,, et al., Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML, N. Engl. J. Med. 2004,351:657-667.
169. Leone A, McBride OW, Weston A, et al. Somatic allelic deletion of nm23 in human cancer. Cancer Res, 1991 ,51(9) : 2490-2493.
170. Cohn KH, Wang FS, Desoto-lapaix F, et al. Association of nm23-H1 allelic deletions with distant metastasis in colorectal carcinoma. Lancet, 1991,338(8769):722-724.
171. Wang L, Patel U, Ghosh L, et al. Mutation in the nm23 gene is associated with metastasis in colorectal cancer. Cancer Res, 1993, 53(4): 717-720.
172．周清华，陈军，孙芝琳，等．nm23-H1等位基因缺失与人非小细胞肺癌转移相关性研究．中国胸心血管外科临床杂志 1998，5(3)：131-134
173．刘伦旭，周清华，孙芝琳等．人肺癌组织中nm23-H_1基因突变研究．中国肺癌杂志．2000；3(3)：201-204
174．汪家政，范明主编．蛋白质技术手册．科学出版社．2000年8月 第一版：42-47．
175. Willert K, Nusse R, Beta-catenin: a Key mediator of Wnt signaling. Curr Opin Genet Dev, 1999, 18(55): 7860-7872.
176. Rubinfeld B, Albert I, Porfiri E, et al. Binding of GSK3 to the APC—Catenin Complex and Regulation of Complex Assembly Science, 1996; 272: 1023-1026.
177. Behrens J, Jerchow BA, Wartele M, et al. Functional Interaction of an Axin Homolog, Conductin, with β-Catenin, APC, and GSK3β. Science, 1998: 280(5365): 596-599
178. Miyoshi Y, Ando H, Nagase H, et al. Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients. Proc Natl Acad Sci USA, 1992, 8(1): 4452-4456.
179. Sansom OJ, Reed KR, Hayes AJ, et al. Loss of APC in vivo immediately perturbs Wnt signaling, differentiation, and migration. Genes Dev. 2004, 18(12): 1385-1390.
180 Woodgett JR. Molecular coloning and expression of glycolgen synthase kinase-3/factor A. EMBO J, 1990, 9(8): 2431-2438.
181 Woodgett JR. cDNA clonging and propertyes of glycolgen synthase kinase-3. Methods Enzymol, 1991, 200: 564-577.
182. Yamamoto H, Kishida S, Kishida M, et al. Phosphorylation of axin, a Wnt signal negative regulator, by glycolgen synthase kinase-3beta regulates its stability. J Biol Chem, 1999, 274(16): 10681-10684.
183. Kishida S, Yamamoto H, Ikeda S. et al. Axin a negative regulator of the Wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stblization of beta-catenin. J Biol Chem, 1998,273(18): 10823-10826.
184. Luo W, Lin SC. Axin: a master scaffold for multiple signaling pathways. Neurosignals, 2004,13(3):99-113
185. Aoki M, Hecht A, Kruse U, et al. Nuclear endpoint of Wnt signaling: neoplasmtic transformation induced by transactivating lymphoid-enhancing factor 1. Proc Natl Acad Sci USA, 1999,96(1): 139-144.
186. Nelson WJ, Nusse R. Convergence of Wnt, (3-catenin and cadherin pathways. Science, 2004,303(5663):1483-1487.
187. Novak A, Hsu SC, Hagestein CL. et al. Cell adhesion and the intergin linked kinase regulated the LEF-1 and beta-catenin signaling pathways . Pro. Natl. Acad Sci.USA , 1998 ,95(8): 4374-4379.
188. Elizabeth P. How a Growth Control Path Takes a Turn to Cancer. Science, 1998, 281(5382): 1438-1441.
189. Chie S, Joseph BW, and Lweis TW. Bridging of beta-catenin and glycogen synthase kinase-3beta by Axin and inhibition of beta-catenin-mediated transcription. Proc. Natl. Acad. Sci. USA , 1998 ,95(6) :3020-3023.
190. Roose J, Gerwitn H, Moniek VB, et al. Synergy Between Tumor Suppressor APC and the beta-catenin/Tcf4 Target Tcfl. Science ,1999 ,285(5435) :1923-1926.
191. Easwaran V , Pish VM, Salimuddin BS. Cross-regulation of beta-caternin-LEF/ TCF and retinoid signaling pathways.Curr Biol, 1999 ,9(23) M415-1418.
192. Embi N, Rylatt D B, Cohen P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMPdependent protein kinase and phosphorylase kinase. Eur J Biochem, 1980, 107: 519-527.
193.Woodgett JR, Cohen P. Multisite phosphorylation of glycogensynthase: molecular basis for the substrate specificity of glycogen synthase kinase-3 and casein kinase-II (glycogen synthase kinase-5). Biochim Biophys Acta, 1984, 788 : 339-347.
194. Ishiguro K, Shiratsuchi A, Sato S,et al.Glycogen synthase kinase 3 beta is identical to tau protein kinase I generating several epitopes of paired helical filaments. FEBS Lett, Jul 1993; 325(3): 167-72.
195. Embi, N. Rylatt, DB. and Cohen, P. Glycogen synthase kinase-3 from rabbit skeletal muscle. Separation from cyclic-AMP-dependent protein kinase and phosphorylase kinase. Eur. J. Biochem. 1980; 107,519-527.
196. Woodgett, JR. and Cohen, P. Multisite phosphorylation of glycogen synthase. Molecular basis for the substrate specificity of glycogen synthase kinase-3 and casein kinase-II (glycogen synthase kinase-5). Biochim. Biophys. Acta 1984;788,339 -347.
197. Frame S, Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem J, 2001,359: 1-16
198. Grimes C A, Jope R S. The multifaceted roles of glycogen synthase kinase 3b in cellular signaling.Prog Neurobiol, 2001,6 5: 391-426
199. Woodgett J R. Judging a protein by more than its name: GSK-3. Sci STKE, 2001, 100: RE12
200. Woodgett J R.Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J, 1990, 9 : 2431-2438
201. Woodgett, JR. Molecular cloning and expression of glycogen synthase kinase-3/factor A. EMBO J. 1990;9:2431 -2438.
202. Ali A. Hoeflich KP and Woodgett JR. Glycogen synthase kinase-3: properties, functions, and regulation. Chem. Rev. 2001; 101,2527 -2540.
203. Adnan Ali, Klaus P, and James R.W. Glycogen synthase kinase-3: properties, function and regulation. Chem. Rev.2001, 101: 2527-2540.
204. Gould TD, Zarate CA, and Manji HK. Glycogen synthase kinase-3: A target for novel bipolar disorder treatments. J Clin Psychiatry 2004:65, 10-21.
205. Frame S. and Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem. J. 2001;359,l-16.
206. Bax B, Carter PS, Lewis C, et al. The structure of phosphorylated GSK-3beta complexed with a peptide, FRATtide, that inhibits beta-catenin phosphorylation. Structure (Camb) 2001 ;9,1143 -1152.
207. Dajani R, Fraser E, Roe S. et al. Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell.2001;105,721 -732.
208. ter Haar E, Coll JT, Austen DA, Structure of GSK3beta reveals a primed phosphorylation mechanism. Nat. Struct. Biol. 2001 ;8, 593-596.
209. Frame S and Cohen P. GSK3 takes centre stage more than 20 years after its discovery. Biochem. J. 2001; 359,1 -16
210. Thomas, GM, Frame S, Goedert M, et al.A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett. 1999;458,247-251.
211. Dajani R, Fraser E, Roe SM,et al. Crystal structure of glycogen synthase kinase 3 beta: structural basis for phosphate-primed substrate specificity and autoinhibition. Cell 2001;105,721-732.
212. Hartigan,JA, Johnson,GV. Transient increases in intracellular calcium result in prolonged site-selective increases in Tau phosphorylation through a glycogen synthase kinase 3β-dependent pathway.J Biol Chem, 1999, 274,21395-21401.
213. Cross D A E, Alessi D R, Cohen P. Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B.Nature, 1995, 378: 785-789.
214. Shaw M, and Cohen P.Role of protein kinase B and the MAP kinase cascade in mediating the EGF-dependent inhibition of glycogen synthase kinase 3 in Swiss 3T3 cells. FEBS Lett.1999, 461, 120-124.
215. He X, Saint-Jeannet J.P, Woodgett J.R, et al. Glycogen synthase kinase-3 and dorsoventral patterning in Xenopus embryos. Nature, 1995, 374, 617-622.
216. Troussard AA, Tan C, Yoganalhan TN,et al.Cell-extracellular matrix interaction stimulate the Ap-1 transcription factor in an intergrin-linked kinase and glycogen synthase kinase 3-dependent manner.Mol Cell Biol, 1999,19:7420-7427.
217. Bhat RV, Shanley J, Correll MP, et al. Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3beta in cellular and animal models of neuronal degeneration. Proc. Natl. Acad. Sci. USA 2000;97,11074 -11079
218. Bijur GN and Jope RS. Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3 beta. J. Biol. Chem. 2001;276,37436 -37442.
219. Morisco C, Seta K, Hardt SE, et al. Glycogen synthase kinase 3Γ regulates GATA4 in cardiac myocytes. J Biol Chem.2001;276:28586-28597.
220. Haq S, Choukroun G, Kang ZB,et al. Glycogen synthase kinase-3Γ is a negative regulator of cardiomyocyte hypertrophy. J Cell Biol. 2000; 151:117-130.
221. Diehl JA, Cheng M, Roussel MF, et al.Glycogen synthase kinase-3β regulates cyclin D1 proteolysis and subcellutar localization. Genes Dev. 1998; 12: 3499-3511.
222. Bijur GN, Jope RS. Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3(?). J Biol Chem. 2001; 276: 37436-37442.
223. Sheelagh F, Philip C.GSK3 takes center stage more than 20 years after its discovery. Biochem J, 2001, 359, 1-16.
224. Gautam N, Richard S. Proapoptotic stimuli induce nuclear accumulation of glycogen synthase kinase-3β. The Journal of Biological Chemistry, 2001, 276: 37436-37442.
225．付军科，周清华，朱文等。nm23-H1基因转染能上调人肺癌细胞株L9981中GSK-3β激酶活性．中国肺癌杂志，2004；7(4)：81-85
226. Miller. J. R. The Writs. Genome Biol. 2002, 3: 3001.
227. Smalley MJ. and Dale TC. Wnt signalling in mammalian development and cancer. Cancer Metastasis Rev. 1999; 18, 215-230.
228. Lako M, Strachan T, Bullen P, et al. Isolation, characterisation and embryonic expression of WNT11, a gene which maps to 11q13.5 and has possible roles in the development of skeleton, kidney and lung. Gene, 1998; 219(1-2): 101-10.
229. Huelsken J and Behrens J. The Writ signalling pathway. J. Cell Sci. 2002; 115, 3977-3978.
230. Seidensticker MJ. and Behrens J. Biochemical interactions in the Wnt pathway. Biochim. Biophys. Acta 2000; 1495, 168-182.
231. Tejpar S, Cassiman JJ, van Cutsem E. The molecular basis of colorectal cancer. Acta Gastro-enterol Belg, 2001, 64 (3): 249-254.
232. van de WeteringM, Sancho E, Verweij C, et al. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell. 2002, 111 (2): 241-250.
233. D'Orazio D, Muller PY, Heinimann K, et al. Overexpression of Wnt target genes in adenomas of familial adenomatous polyposis patients. Anticancer Res, 2002; 22 (6A):3409-3414.
234. Ginger RS, Dalton EC, Ryves WJ, et al. Glycogen synthase kinase-3 enhances nuclear export of a dictyostelium STAT protein. EMBO J. 2000;19:5483-5491.
235. Cohen P, Frame S. The renaissance of GSK3. Nat Rev Mol Cell Biol.2001;2:769-776.
236. Peifer M, Polakis P. Wnt signaling in oncogenesis and embryogenesis——a look outside the nucleus. Science ,2000 ,287 :1606—1609
237. Hinoi, T., Yamamoto, H., Kishida, M., et al.. Complex formation of adenomatous polyposis coli gene product and axin facilitates glycogen synthase kinase-3 beta-dependent phosphorylation of beta-catenin and down-regulates beta-catenin. J. Biol. Chem. 2000; 275,34399 -34406
238. Ikeda S, Kishida S, Yamamoto H, et al.Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent phosphorylation of beta-catenin. EMBO J. 1998;17,1371 -1384.
239. Jho E, Lomvardas S and Costantini F. A GSK3beta phosphorylation site in axin modulates interaction with beta-catenin and Tcf-mediated gene expression. Biochem. Biophys. Res. Commun 1999;266,28-35.
240. Yamamoto H, Kishida S, Kishida M, et al.Phosphorylation of axin, a Wnt signal negative regulator, by glycogen synthase kinase-3beta regulates its stability. J. Biol. Chem. 1999;274,10681 -10684.
241. Rubinfeld B, Albert I, Porfiri E, et al. Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 1996; 272,1023 -1026.
242. Kim L, Kimmel AR. GSK3, a master switch regulating cell-fate specification and tumor-igenesis. Curr Opin Genet Dev. 2000; 10:508-514.
243. Imahori K, Uchida T. Physiology and pathology of tau protein kinases in relation to Alzheimer's disease. J Biochem (Tokyo). 1997;121:179-188.
244. Miller JR, Hocking AM, Brown JD, Moon RT. Mechanism and function of signal transduction by the Wnt/βcatenin and Wnt/Ca2p pathways.Oncogene. 1999; 18:7860-7872.
245. Fiol CJ, Mahrenholz AM, Wang Y, Roeske RW, Roach PJ. Formation of protein kinase recognition sites by covalent modification of the substrate: molecular mechanism for the synergistic action of casein kinase II and glycogen synthase kinase 3. J Biol Chem. 1987;262:14042-14048.
246. Plyte SE, Hughes K, Nikolakaki E, Pulverer BJ, Woodgett JR. Glycogen synthase kinase-3: functions in oncogenesis and development. Biochim Biophys Acta. 1992; 1114:147-162.
247. Porter CM, Havens MA, Clipstone NA. Identification of amino acid residues and protein kinases involved in the regulation of NFATc subcellular localization. J Biol Chem. 2000;275:3543-3551.
248. ter Haar E, Coll JT, Austen DA, Hsiao HM, Swenson L, Jain J. Structure of GSK3Γ reveals a primed phosphorylation mechanism. Nat Struct Biol. 2001;8: 593-596.
249. Woods YL, Cohen P, Becker W, Jakes R, Goedert M, Wang X, Proud CG The kinase DYRK phosphorylates protein-synthesis initiation factor elF2B- at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase. Biochem J. 2001 ;355:609-615.
250. Amit S, Hatzubai A, Birman Y,et al. Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev. 2002;16,1066 -1076.
251. Hagen T, di Daniel E, Culbert AA.et al. Expression and characterization of GSK-3 mutants and their effect on beta-catenin phosphorylation in intact cells. J. Biol. Chem. 2002:277,23330 -23335.
252. Hagen T. and Vidal-Puig A. Characterisation of the phosphorylation of beta-catenin at the GSK-3 priming site Ser45. Biochem. Biophys. Res. Commun. 2002;294,324 -328.
253. Liu C, Li Y, Semenov M, et al.Control of beta-catenin phosphorylation/degradation by a dual-kinase mechanism. Cell 2002; 108,837 -847.
254. Sakanaka C. Phosphorylation and regulation of beta-catenin by casein kinase I epsilon. J. Biochem. (Tokyo) 2002; 132,697 -703.
255. Yanagawa S, Matsuda Y, Lee JS. Casein kinase I phosphorylates the Armadillo protein and induces its degradation in Drosophila.2002;EMBO J. 21,1733 -1742.
256. Schwarz-Romond T, Asbrand C, Bakkers J,et al. The ankyrin repeat protein Diversin recruits Casein kinase Iepsilon to the beta-catenin degradation complex and acts in both canonical Wnt and Wnt/JNK signaling. Genes Dev. 2002; 16,2073 -2084.
257. Farr GH, 3rd, Ferkey DM, Yost C,et al. Interaction among GSK-3, GBP, axin, and APC in Xenopus axis specification. J. Cell Biol. 2002; 148,691 -702.
258. Ferkey DM and Kimelman D. Glycogen synthase kinase-3 beta mutagenesis identifies a common binding domain for GBP and Axin. J. Biol. Chem. 2002;277,16147 -16152.
259. Fraser E, Young N, Dajani R,et al. Identification of the Axin and Frat binding region of glycogen synthase kinase-3. J. Biol. Chem. 2002;277,2176 -2185.
260. Sumoy L, Kiefer J and Kimelman D. Conservation of intracellular Wnt signaling components in dorsal-ventral axis formation in zebrafish. Dev. Genes Evol. 2002;209, 48-58.
261. Yost C, Farr GH, 3rd, Pierce SB,et al. GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis. Cell 1998;93,1031 -1041.
262. Thomas GM, Frame S, Goedert M,et al. A GSK3-binding peptide from FRAT1 selectively inhibits the GSK3-catalysed phosphorylation of axin and beta-catenin. FEBS Lett. 1999; 458, 247-251.
263. Franca-Koh J, Yeo M, Fraser E, et al. The regulation of glycogen synthase Kinse-3 nuclear export by Frat/GBP. J. Biol. Chem. 2002; 277, 43844-43848.
264. Ding VW, Chen RH and McCormick E Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling. J. Biol. Chem. 2000; 275, 32475-32481.
265. Yuan H, Mao J, Li L. et al. Suppression of glycogen synthase kinase activity is not sufficient for leukemia enhancer factor-1 activation. J. Biol. Chem. 1999; 274, 30419-30423.
266．王瑞年．Wnt信号传导与癌症．中国肿瘤，2002；11(10)：594-596．
267. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenolmenon with wide ranging implicateons in tissue kinetics. Br J Cancer. 1972, 26: 239-257
268. Stetler-Stevenson WG, Aznavoorian S, and Liotta LA. Tumor cell interactions with the extracellular matrix during invasion and metastasis. Annu Rev Cell Biol, 1993; 9: 541-73.
269. Gilles AM , Presecan E, Vonica A et al. Nucleoside diphosphate kinase from human erythrocytes: Structural characterization of the two polypeptide chains respondible for heterogeneity, of hexameric enzyme. J Biol Chem, 1991; 266: 8784
270. You L. He B, Xu Z, et al.. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells, Oncogene 2004; 23: 6170-6174.
271．车国卫，周清华，朱文等．nm23-H1基因逆转人高转移大细胞肺癌细胞L9981转移表型的分子机制．癌症，2005，24(3)：278—284
272．高庆蕾，马丁．nm23-H_1基因表达与卵巢转移的相关性．癌症．2004；23(6)：650—654
273. Leone A, Flatow U, VanHoutte K et al. 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 1993; 8: 2325-2333.
274. Bhujwalla Z, Aboagye E, Gilles R et al. nm23-transfected MDAMB-435 human breast carcinoma cells form tumors with altered phospholipid metabolism and pH: A 31P nuclear magnetic resonance study in vivo and in vitro. Magn Res Med 1999; 41: 897-903.
275. Russell R, Pedersen A, Kantor J et al. Relationship of nm23 to proteolytic factors, proliferation and motility in breast cancer tissues and cell lines. Br J Cancer 1998; 78: 710-717.
276. Fukuda M, Ishii A, Yasutomo Y et al. Metastatic potential of rat mammary adenocarcinoma cells associated with decreased expression of nucleoside diphosphate kinase/nm23: Reduction by transfection of NDP Kinase a isoform, an nm23-H2 gene homolog. Int J Cancer 1996; 65: 531-537.
277. Leone A, Flatow U, King CR et al. Reduced tumor incidence,metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell 1991; 65: 25-35.
278. Baba H, Urano T, Okada K et al. Two isotypes of murine nm23/Nucleoside Diphosphate Kinse, nm23-M1 and nm23-M2, are involved in metastatic suppression of a murine melanoma line. Cancer Res 1995; 55: 1977-1981.
279. Parhar RS, Shi Y, Zou M et al. Effects of cytokine mediated modulation of nm23 expression on the invasion and metastatic behavior of B16F10 melanoma cells. Int J Cancer 1995; 60: 204-210.
280. Miele ME, Rosa ADL, Lee JH et al. Suppression of human melanoma metastasis following introduction of chromosome 6 is independent of NMEl (nm23). Clin Exp Metastasis 1997; 15:259-265.
281. Tagashira H, Hamazaki K, Tanaka N et al. Reduced metastatic potential and c-myc overexpression of colon adenocarcinoma cells (Colon 26 line) transfected with nm23-R2 rat nucleoside diphosphate kinase a isoform. Int J Mol Med 1998; 2: 65-68.
282. Miyazaki H, Fukuda M, Ishijima Y et al. Overexpression of nm23-H2/NDP Kinase B in a human oral squamous cell carcinoma cell line results in reduced metastsis, differentiated phenotype in the metastatic site, and growth factor-independent proliferative activity in culture. Clin Cancer Res 1999; 5: 4301-4307.
283. Liotta LA. Tumor invasion and metastases: role of the basement membrane. Am J Pathol, 1986, 117: 339-348.
284. Albini A, Iwamoto Y, Kleinman HK, et al. A rap id in vitro assay for quantitating the invasive potential of tumor cells. Cancer Res, 1987, 47: 3239-3245.
285．周清华，王艳萍、车国卫等．人大细胞肺癌细胞系NL9980和L9981的建立及其生物学特性研究．中国肺癌杂志．2003；6(6)：464-468
286．车国卫，周清华，王艳萍等．人肺癌细胞株L9981-nm23-H1的建立．中国肺癌杂志．2004，7(3)：187-189
287. Liotta LA. Cancer cell invasion and metastasis. Scientific American, 1992, 266(2): 34—41.
288. Liotta LA, Rao CN, Barsky SH. Tumor invasion and the extracellular matrix. Lab Invest. 1983; 49(6): 636-49.
289. Hand PH, Thor A, Schlom J, Expression of laminin receptor in normal and carcinomatous human tissues as defined by a monoclonal antibody. Cancer Res., 1985; 45: 2713-2719.
290. Turner S, Sherratt JA. Intercellular adhesion and cancer invasion: a discrete simulation using the extended Potts model. J Therol Biol, 2002; 216: 85-100.
291. Bremnes RM, Veve R, Hirsch FR, et al. The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastsis, and prognosis. Lung Cancer, 2002, 36: 115-124.
292．付军科，周清华，朱文，等．转染nm23-H1基因靶向阻断人大细胞肺癌细胞株L9981 Wnt 信号传导通路．中国肺癌杂志．2004；7(4)：294-297
293．郑海霞，申尔兰，周清华等．nm23-H1基因逆转肺癌细胞转移表型的功能鉴定．北京大学学报(医学版)．2005；37(3)：335—336
294. Guo HB, Liu F, Zhao JH, et al. Down-regulation of N-acetylglucosaminyl transferase Ⅴ by tumorigenesis or metastasis suppressor gene and its relation to metastatic potential of human hepatocarcinoma cells. J Cell Biochem, 2000, 79: 370-385
295. Kantor JD, McCormick B, Steeg PS, et al. Inhibition of cell motility after nm23 transfection of human and murine tumor cells. Cancer Res. 1993; 53: 1971-1973.
296. Nickerson JA, Wells WW. The microtubule-associated nucleoside diphosphate kinase. J Biol Chem, 1984, 259(18): 11297-11300.
297. Leone A, Flatow U, King CR. Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells. Cell, 1991; 65(1): 25-35.
298. Liotta LA, Steeg PS. Clues to the function of nm23 and Awd proteins in development, signal transduction and tumor metastasis provided by studies of dictyostelium discoideum. J Natl Cancer Inst, 1990, 82(14): 1170-1172.
299. Golden A, Benedict M, Shearn A, et al. Nucleoside diphosphate kinase, nm23 and tumor metastasis: possible biochemical mechanisms. In: Benz C, Liu E eds. Oncogenes and Tumor Sppressor Genes in Human Malignancies. Kluwr Academic Phblishers, 1993. 345-358.
300. Gilles AM, Presecan E, Vonica A, et al. Nucleoside diphosphate kinase from human erythrocytes. Structural characterization of the two polypeptide chains responsible for heterogeneity of the hexameric enzyme. J. Biol. Chem. 1991; 266: 8784-8789.
301．周清华，车国卫，覃扬，等．nm232H1基因逆转肺癌转移表型及其分子机制的实验研究． 中国肺癌杂志，2003；6(2)：141-143．
302. Bogenrieder T, Herlyn M. Axis of evil: molecular mechanisms of cancer metastasis. Oncogene, 2003, 22 (42): 6524-6536
1. Smith W, Khuri FR, The care of the lung cancer patient in the 21 st century: a new age, Semin. Oncol. 2004;31:11-15
2. Nusse R, Varmus HE, Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome, Cell 1982;31:99-109.
3. Pennisi E. How a growth control path takes a wrong turn to cancer? Science, 1998, 281: 1438-1439,1441.
4. Dierick H and Bejsovec A. Cellular mechanisms of wingless/Wnt signal transduction.Curr Top Dev Biol.1999;43:153-190.
5. Bienz M,Clevers H, Linking colorectal cancer to Wnt signaling, Cell 2000;103:311-320.
6. Polakis P, Wnt signaling and cancer, Genes Dev. 2000; 14:1837-1851.
7. Morin PJ, Sparks AB, Korinek V, et al.. Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC, Science 199;275:1787-1790.
8. Korinek V, Barker N, Morin PJ, et al.. Constitutive transcriptional activation by a beta-catenin-Tcf complex in APCK/Kcolon carcinoma, Science 1997;275:1784-1787.
9. Rhee CS, Sen M, Lu D, et aLWnt and frizzled receptors as potential targets for immuno-therapy in head and neck squamous cell carcinomas, Oncogene 2002;21:6598-6605.
10. Weeraratna AT, Jiang Y, Hostetter G,et al.. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma, Cancer Cell.2002;1:279-288.
11. Lu D, Zhao Y, Tawatao R,et al..Activation of the Wnt signaling pathway in chronic lymphocytic leukemia, Proc. Natl Acad. Sci. USA. 2004;101:3118—3123.
12. Wodarz A, Nusse R. Mechanisms of Wnt signaling in development. Annual Reviews in Cell and Development Biology, 1998, 14: 59-88.
13. Gumbiner BM.. Propagation and localization of Wnt signaling. Curr Opin Genet Devel, 1998. 8: 430-435
14. Peifer M, Polakis P: Wnt signaling in onceogenesis and embryogenesis-a look outside the nucleus. Science 2000. 287: 1606-1609.
15. Kuhl M, Sheklahl LC, Park M, et al. The Wnt/Ca2~+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet 2000, 16: 279-283.
16. Peifer M, McEwen DG: The ballet of morphogenesis: unveiling the hidden choreographers. Cell 2002, 109: 271-274.
17. Capdevila J, Belmonte JCI: Extracellular modulation of the Hedgehog, Wnt and TGF-βsignaling pathways during embryonic development. Curr Opin Genet Dev 1999, 9: 427-433.
18. Saneyoshi T, Kume S, Amasaki Y, et al. The Wnt/calcium pathway activeates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature 2002, 417: 295-299.
19. Malbon CC, Wang H, Moon RT: Wnt signallyng and hetertrimeric G-Proteins: strange bedfellows or a classic romance? Biochem Biophys Res commun 2001, 287: 589-593.
20. Kuhi M, Geis K, Sheldahl LC, et al. Antagonistic regulation of convergent extension movements in Xenopus by Wnt/beta-catenin and Wnt/Ca~(2+) signaling. Mech Dev 2001, 106: 61-76.
21. Winktbauer R, Medina A, Swain RK, et al. Frizzled-7 signaling controls tissue separation during Xenopus. Nature 2001, 413: 856-860.
22. Sokol S: Arole for Wnts in morphogenesis and tissue polarity. Nat Cell Biol 2000, 2: E124-E125.
23. Akiyama T., Wnt/beta-catenin signaling, Cytokine Growth Factor Rev. 2000.11: 273-282.
24. Korinek V, Barker N, Moerer P, et al.. Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4, Nat.Genet. 1998; 19:379-383.
25. Brennan KR, Brown AM, Wnt proteins in mammary development and cancer, J. Mammary Gland Biol. Neoplasia 2004;9:119-131.
26. Pandur P, Lasche M, Eisenberg LM,Kuhl M. Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis, Nature ,2002;418:636-641.
27. Reya T, Duncan AW, Ailles L, et al.. A role for Wnt signalling in self-renewal of haematopoietic stem cells, Nature 2003;423:409-414.
28. Rijsewijk F, Schuermann M, Wagenaar K,et al.. The Drosophila homolog of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless, Cell 1987;50:649-657.
29. Morrisey KK, Wnt signaling and pulmonary fibrosis, Am.J. Pathol. 2003;162:1393-1397.
30. Yamaguchi TP, Bradley A, McMahon AP,et al. A Wnt5a pathway underlies outgrowth of multiple structures in the vertebrate embryo, Development 1999:126:1211-1223.
31. Weidenfeld J, Shu W, Zhang L, et al. The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium, J. Biol. Chem. 2002;277:21061-21070.
32. Li C, Xiao J, Hormi K,et al.. Wnt5a participates in distal lung morphogenesis, Dev. Biol. 2002; 248:68-81.
33. Shu W, Jiang YQ, Lu MM, et al..Wnt7b regulates mesenchymal proliferation and vascular develop- ment in the lung, Development 2002;129:4831-4842.
34. Bonner AE, Lemon WJ, You M, Gene expression signatures identify novel regulatory pathways during murine lung development: implications for lung tumorigenesis, J. Med. Genet. 2003;40:408-417.
35. Chilosi M, Poletti V, Zamo A, et al..Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis, Am. J. Pathol.2003; 162:1495-1502.
36. Keith WN. From stem cells to cancer: balancing immortality and neoplasia, Oncogene 23 (2004) 5092-5094.
37. Reya T, Duncan AW, Ailles L, et al., A role for Wnt signalling in self-renewal of haematopoietic stem cells, Nature 423 (2003) 409-414.
38. Sato N, Meijer L, Skaltsounis L.et al. Maintenance of pluripotency in human and mouse embryonic stem cells through activation of Wnt signaling by a pharmacological GSK-3-specific inhibitor, Nat. Med. 10 (2004) 55-63.
39. Ross S E , Hemati N , Longo KA , et al . Inhibition of adipogenesis by Wnt signaling. Science , 2000 , 289 (5481): 950—953
40. Reya T, OpRiordan M, Okamura R , et al . Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism.lmmunity , 2000 , 13 (1): 15-24
41. Chenn A , Walsh C A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science , 2002 , 297 (5580): 365-369
42. Chenn A , Walsh C A. Regulation of cerebral cortical size by control of cell cycle exit in neural precursors. Science , 2002 , 297 (5580): 365-369
43. Jamieson CH, Ailles LE,.Dylla SJ,, et al., Granulocyte-macrophage progenitors as candidate leukemic stem cells in blast-crisis CML, N. Engl. J. Med. 2004,351:657-667.
44. Korinek V, Barker N, Moerer P, et al., Depletion of epithelial stem-cell compartments in the small intestine of mice lacking Tcf-4, Nat.Genet. 1998,19:379-383.
45. Gat U. DasGupta R, Degenstein L,et al. De Novo hair follicle morphogenesis and hair tumors in mice expressing a truncated beta-catenin in skin, Cell. 1998; 95:605-614.
46. van de Wetering M, Sancho,E, Verweij C, et al., The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells, Cell 2002; 111:241-250.
47. Fuchs E and Segre JA.Stem cells: a new lease on life.Cell.2000; 100(1): 143-55.
48. Bienz M,Clevers H. Linking colorectal cancer to Wnt signaling .Cell ,2000,103 :3112320.
49. Reya T, Morrison SJ, Clarke MF, et al.Stem cells, cancer, and cancer stem cells, ature. 2001; 414(6859): 105-11.
50. Zhu AJ,Watt EM.β-catenin signaling modulates proliferative potential of human epidermal keratino- cytes independently of intercellular adhesion Development , 1999 , 126 :2258-2298.
51. Willert J ,Epping M,Pollack JR , et al . A transcriptional response to Wnt protein in human embryonic cancinoma cells.BMC Dev Biol ,2002 ,2(1):8-15.
52. Nusse R,Varmus HK, Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome, Cell 1982;31:99-109.
53. Katoh M, Expression and regulation of WNT1 in human ancer: up-regulation of WNT1 by beta-estradiol in MCF-7cells, Int. J. Oncol. 2003;22:209-212.
54. Wong SC, Lo SF, Lee KC,et al. Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours, J. Pathol.2002;196:145-153.
55. Chen S, Guttridge DC, You Z,et al.. Wnt-1 signaling inhibits apoptosis by activating beta-catenin/T cell factor-mediated transcription, J. Cell Biol. 2001; 152:87-96
56. He B, You L,Uematsu K,et al., A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells, Neoplasia 2004;6:7-14.
57. Katoh M, Frequent up-regulation of WNT2 in primary gastric cancer and colorectal cancer, Int. J. Oncol. 2001; 19:1003-1007.
58. Yoshida MC, Wada M, Satoh H, et al.. Human HST1 (HSTF1) gene maps to chromosome band 11q13 and coamplifies with the INT2 gene in human cancer, Proc. Natl Acad. Sci. USA 1988:85:4861-4864.
59. Roelink H, Wagenaar E, Nusse R, Amplification and proviral activation of several Wnt genes during progression and clonal variation of mouse mammary tumors, Oncogene 1992:7:487-492.
60. Nessling M, Solinas-Toldo S, Wilgenbus KK,et al.. Mapping of chromosomal imbalances in gastric adenocarcinoma revealed amplified protooncogenes MYCN,MET, WNT2, and ERBB2, Genes Chromosomes Cancer 1998;23:307-316.
61. Katoh M, Kirikoshi H, Terasaki H,et al. WNT2B2 mRNA, up-regulated in primary gastric cancer, is a positive regulator of the WNT-beta-catenin-TCF signaling pathway, Biochem. Biophys. Res. Commun. 2001;289:1093-1098.
62. Vider BZ, Zimber A, Chastre K, et al.. Evidence for the involvement of the Wnt 2 gene in human colorectal cancer, Oncogene 1996;12:153—158.
63. Holcombe RP, Marsh JL,Waterman ML,et al..Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma, Mol. Pathol.2002;55:220-226.
64. Katoh M, Differential regulation of WNT2 and WNT2B amonghuman cancer, Int. J. Mol. Med. 2001 ;8:657-660.
65. Pham K, Milovanovic T, Barr RJ, et al.. Wnt ligand amongmalignant melanoma: pilot study indicating correlation with histopathological features, Mol. Pathol. 56 (2003) 280-285.
66. You L. He B, Xu Z.et al.. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells,Oncogene 2004;23:6170-6174.
67. Calvo R, West J, Franklin W,et al., Altered HOX and WNT7A amonghuman lung cancer, Proc. Natl Acad. Sci. USA 2000;97:12776-12781.
68. Ohira T, Gemmill RM, Ferguson K,et al.. WNT7a induces E-cadherin in lung cancer cells, Proc. Natl Acad. Sci. USA 2003; 100:10429-10434.
69. Kengaku M, Capdevila J, Rodriguez-Esteban C,et al.. Distinct WNT pathways regulating AER formation and dorsoventral polarity in the chick limb bud, Science 1998;298:1274-1277.
70 . Moon RT, Brown JD, Torres M, WNTs modulate cell fate and behavior during vertebrate development,Trends Genet. 1997; 13:157-162.
71. Saitoh T, Mine T, Katoh M, Frequent up-regulation of WNT5A mRNA in primary gastric cancer, Int. J. Mol. Med. 2002;9:515-519.
72. Weeraratna AT, Jiang Y, Hostetter G, et al.. Wnt5a signaling directly affects cell motility and invasion of metastatic melanoma, Cancer Cell 2002 1:279-288.
73. Liang H, Chen Q, Coles AH, et al.. Wnt5a inhibits B cell proliferation and functions as a tumor suppressor in hematopoietic tissue, Cancer Cell 2003;4 349-360.
74. Nakano T, Tani M, Ishibashi Y, et al.. Biological properties and gene expression associated with metastatic potential of human osteosarcoma, Clin. Exp. Metastasis 2003;20:665-674.
75. Zeng L, Fagotto F, Zhang T, et al., The mouse fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation, Cell 1997;90:181—192.
76. Ponting CP, Phillips C, Davies KE, PDZ domains: targeting signalling molecules to sub-membranous sites, Bioessays 1997; 19:469-479.
77. Ponting CP, Bork P, Pleckstrin's repeat performance: a novel domain in G-protein signaling?, Trends Biochem. Sci. 1996;21:245-246.
78. Uematsu K, He B, You L,et al.. Activation of the Wnt pathway in non small cell lung cancer: evidence of dishevelled overexpression, Oncogene 2003;22:7218—7221.
79. Uematsu K, Kanazawa S, You L, et al.Wnt pathway activation in mesothelioma: evidence of dishevelled overexpression and transcriptional activity of beta-catenin, Cancer Res. 2003:63:4547-4551.
80. Wharton Jr. KA. Runnin' with the Dvl: proteins that associate with Dsh/Dvl and their significance to Wnt signal transduction, Dev. Biol. 2003;253:l—17.
81. Hommura F, Furuuchi K, Yamazaki K,et al.. Increased expression of beta-catenin predicts better prognosis in nonsmall cell lung carcinomas, Cancer 2002;94:752-758.
82. Retera JM, Leers MP, Sulzer MA,et al. The expression of beta-catenin in non-small-cell lung cancer: a clinicopathological study, J. Clin. Pathol. 1998;51: 891-894.
83. Kase S, Sugio K, Yamazaki K, et al.. Expression of E-cadherin and beta-catenin in human non-small cell lung cancer and the clinical significance.Clin. Cancer Res. 2000;6:4789-4796
84. Shigemitsu K, Sekido Y, Usami N,et al.. Genetic alteration of the beta-catenin gene (CTNNB1) in human lung cancer and malignant mesothelioma and identification of a new 3p21.3 homozygous deletion, Oncogene 2001;20:4249-4257.
85. Nakatani Y, Masudo K, Miyagi Y.et al.. Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules, Mod. Pathol. 2002;15:617-624.
86. Cooper CA, Bubb VJ, Smithson N,et al.. Loss of heterozygosity at 5q21 in non-small cell lung cancer: a frequent event but without evidence of apc mutation, J. Pathol. 1996;180:33—37.
87. Horii A, Nakatsuru S, Miyoshi Y,et al.. Frequent somatic mutations of the APC gene In human pancreatic cancer, Cancer Res. 1992;52:6696-6698.
88. Furuuchi K, Tada M, Yamada H,et al..Somatic mutations of the APC gene in primary breast cancers, Am. J. Pathol. 2000; 156:1997-2005
89 . Ohgaki H, Kros JM, Okamoto Y,et al.. APC mutations are infrequent but present in human lung cancer, Cancer Lett. 2004;207:197-203.
90. Veeman MT,Axelrod JD, Moon RT, A second canon. Functions and mechanisms of beta-catenin-independent Wnt signaling, Dev. Cell 2003;5:367-377.
91. Habas R, Kato Y, He X, Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daaml, Cell 2001 ;107: 843-854.
92. Choi SC, Han JK, Xenopus Cdc42 regulates convergent extension movements during gastrulation through Wnt/Ca2C signaling pathway, Dev. Biol. 2002;244:342-357.
93. Penzo-Mendez A, Umbhauer M, Djiane A,et al.. Activation of Gbetagamma signaling downstream of Wnt-11/Xfz7 regulates Cdc42 activity during Xenopus gastrulation, Dev. Biol. 2003; 257:302-314.
94. Hordijk PL, ten Klooster JP, van der Kammen RA,et al..Inhibition of invasion of epithelial cells by Tiam1-Rac signaling, Science 1997;278:1464-1466.
95 . Soon LL, Yie TA, Shvarts A,et al.. Overexpression of WISP-1 downregulated motility and invasion of lung cancer cells through inhibition of Rac activation, J. Biol. Chem. 2003;278:11465-11470.
96 . Tao W, Pennica D, Xu L, et al.. Wrchl, a novel member of the Rho gene family that is regulated by Wnt-1, Genes Dev. 2001; 15:1796-1807.
97. Habas R, Dawid IB, He X, Coactivation of Rac and Rho by Wnt/Frizzled signaling is required for vertebrate gastrulation, Genes Dev. 2003; 17:295-309.
98. Allal C, Favre G, Couderc B, et al.. RhoA prenylation is required for promotion of cell growth and transformation and cytoskeleton organization but not for induction of serum response element transcription, J. Biol. Chem. 2000;275:31001-31008.
99. Mazieres J, Antonia T, Daste G, et al.. Loss of RhoB amonghuman lung cancer progression, Clin. Cancer Res. 2004; 10:2742-2750.
100. Ikoma T, Takahashi T, Nagano S,et al.. A definitive role of RhoC in metastasis of orthotopic lung cancer in mice, Clin. Cancer Res. 2004;10:1192-1200.
101. del Peso L, Hernandez-Alcoceba R, Embade N,et al. Rho proteins induce metastatic properties in vivo, Oncogene 1997; 15:3047-3057.
102. Yao R, Wang Y, Lubet RA,et al.. Differentially expressed genes associated with mouse lung tumor progression, Oncogene 2002;21:5814-5821.
103. Malliri A, Collard JR, Role of Rho-family proteins in cell adhesion and cancer, Curr. Opin. Cell Biol. 2003;15:583-589.
104. Boutros M, Paricio N, Strutt DI,et al.. Dishevelled activates JNK and discriminates between JNK pathways in planar polarity and wingless signaling, Cell 1998;94:109-l 18.
105. Moriguchi T, Kawachi K, Kamakura S,et al.. Distinct domains of mouse dishevelled are responsible for the c-Jun N-terminal kinase/stress-activated protein kinase activation and the axis formation in vertebrates, J. Biol. Chem. 1999;274:30957-30962.
106. You L, He B, Uematsu K, et al..Inhibition of Wnt-1 signaling induces apoptosis in betacatenin-deficient mesothelioma cells, Cancer Res. 2004;64:3474-3478.
107. Kawano Y, Kypta R, Secreted antagonists of the Wnt signalling pathway, J. Cell Sci. 2003; 116:2627-2634.
108. Ko J. Ryu KS, Lee YH,et al.. Human secreted frizzled-related protein is downregulated and induces apoptosis in human cervical cancer, Exp. Cell Res. 2002;280:280-287
109. Ugolini F, Charafe-Jauffret E, Bardou VJ, et al.. WNT pathway and mammary carcinogenesis: loss of expression of candidate tumor suppressor gene SFRPl in most invasive carcinomas except of the medullary type, Oncogene. 2001 ;20:5810-5817.
110. To KF, Chan MW, Leung WK,et al.. Alterations of frizzled (Fz3) and secreted frizzled related protein (hsFRP) amonggastric cancer, Life Sci. 2001 ;70:483-489.
111. Suzuki H, Gabrielson K,Chen W, et al.. A genomic screen for genes upregulated by demethylation and histone deacetylase inhibition in human colorectal cancer, Nat. Genet. 2002;31:141-149.
112. Suzuki H, Watkins DN, Jair KW, et al.. Epigenetic inactivation of SFRP genes allows constitutive WNT signaling in colorectal cancer. Nat Genet. 2004 ;36(4):417-22..
113. Caldwell GM, Jones C, Gensberg K, et al. The Wnt antagonist sFRPl in colorectal tumorigenesis, Cancer Res. 2004;64:883-888.
114. Hsieh JC, Kodjabachian L, Rebbert ML, et al.. A new secreted protein that binds to Wnt proteins and inhibits their activities, Nature 1999;398:431-436.
115. Wissmann C, Wild PJ, Kaiser S, et al.. WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer, J. Pathol. 2003;201:204-212.
116. Mazieres J, He B, You L, et al..Wnt inhibitory factor-1 is silenced by promoter hyperme-thylation in human lung cancer, Cancer Res. 2004;64:4717-4720.
117. Wong SC, Lo SF, Lee KC,et aL.Expression of frizzled-related protein and Wnt-signalling molecules in invasive human breast tumours, J. Pathol. 2002; 196:145-153.
118. Lee AY, He B, You L,et aL.Expression of the secreted frizzled-related protein gene family is downregulated in human mesothelioma, Oncogene 2004; 23(39): 6672-6676
119. Fedi P, Bafico P, Nieto Soria A, et al.. Isolation and biochemical characterization of the human Dkk-1 homologue, a novel inhibitor of mammalian Wnt signaling, J. Biol. Chem. 1999; 274: 19465-19472.
120. Tsuji T, Miyazaki M, Sakaguchi M, et al. A REIC gene shows down-regulation in human immortalized cells and human tumor-derived cell lines, Biochem. Biophys. Res. Commun. 2000; 268: 20-24.
121. Nozaki I, Tsuji T, Iijima C, et al.. Reduced expression of REIC/Dkk-3 gene in non-small cell lung cancer, Int. J. Oncol. 2001; 19: 117-121
122. Tsuji T, Nozaki I, Miyazaki M, et al.. Antiproliferative activity of REIC/Dkk-3 and its significant down-regulation in non-small-cell lung carcinomas, Biochem. Biophys. Res. Commun. 2001; 289: 257-263.
123. Kobayashi K, Ouchida M, Tsuji T, et al.. Reduced expression of the REIC/Dkk-3 gene by promoter-hypermethylation in human tumor cells, Gene 282 (2002) 151-158.