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Journal of Hematology & Oncology
Published in: Journal of Hematology & Oncology 1/2010

Open Access 01-12-2010 | Review

Role of Wnt canonical pathway in hematological malignancies

Authors: Xueling GE, Xin Wang

Published in: Journal of Hematology & Oncology | Issue 1/2010

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Abstract

Wnt canonical signaling pathway plays a diverse role in embryonic development and maintenance of organs and tissues in adults. It has been observed that Wnt/β-catenin signaling pathway is involved in the pathogenesis of many carcinomas. Moreover, Wnt/β-catenin pathway has been revealed to be associated with angiogenesis. Wnt canonical pathway signaling has great potential as a therapeutic target. It has been disclosed that some hematological malignancies, such as chronic lymphocytic leukemia, mantle cell lymphoma, may occur partly due to the constitutive activation of Wnt canonical signaling pathway. This review will summarize the latest development in Wnt canonical signaling pathway and its roles in tumorigenesis and angiogenesis.
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Literature
1.
Sidow A: Diversification of the Wnt gene family on the ancestral lineage of vertebrates. Proc Natl Acad Sci USA. 1992, 89: 5098-5102. 10.1073/pnas.89.11.5098.PubMedCentralCrossRefPubMed
2.
Rubinfeld B, Albert I, Porfiri E, Fiol C, Munemitsu S, Polakis P: Binding of GSK3beta to the APC-beta-catenin complex and regulation of complex assembly. Science. 1996, 272: 1023-1026. 10.1126/science.272.5264.1023.CrossRefPubMed
3.
Peifer M: Beta-catenin as oncogene: the smoking gun. Science. 1997, 275: 1752-1753. 10.1126/science.275.5307.1752.CrossRefPubMed
4.
Morin PJ, Sparks AB, Korinek V, Barker N, Clevers H, Vogelstein B, Kinzler KW: Activation of beta-catenin-Tcf signaling in colon cancer by mutations in beta-catenin or APC. Science. 1997, 275: 1787-1790. 10.1126/science.275.5307.1787.CrossRefPubMed
5.
Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P: Stabilization of beta-catenin by genetic defects in melanoma cell lines. Science. 1997, 275: 1752-1753. 10.1126/science.275.5307.1790.CrossRef
6.
Chesire DR, Ewing CM, Sauvageot J, Bova GS, Isaacs WB: Detection and analysis of beta-catenin mutations in prostate cancer. Prostate. 2000, 45: 323-334. 10.1002/1097-0045(20001201)45:4<323::AID-PROS7>3.0.CO;2-W.CrossRefPubMed
7.
de la Taille A, Rubin MA, Chen MW, Vacherot F, de Medina SG, Burchardt M, Buttyan R, Chopin D: Beta-catenin-related anomalies in apoptosis-resistant and hormone-refractory prostate cancer cells. Clin Cancer Res. 2003, 9: 1801-1807.PubMed
8.
Jeays-Ward K, Hoyle C, Brennan J, Dandonneau M, Alldus G, Capel B, Swain A: Endothelial and steroidogenic cell migration are regulated by WNT4 in the developing mammalian gonad. Development. 2003, 130: 3663-3670. 10.1242/dev.00591.CrossRefPubMed
9.
Wu R, Zhai Y, Fearon ER, Cho KR: Diverse mechanisms of betacatenin deregulation in ovarian endometrioid adenocarcinomas. Cancer Res. 2001, 61: 8247-8255.PubMed
10.
Rask K, Nilsson A, Brannstrom M, Carlsson P, Hellberg P, Janson PO, Hedin L, Sundfeldt K: Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3beta. Br J Cancer. 2003, 89: 1298-1304. 10.1038/sj.bjc.6601265.PubMedCentralCrossRefPubMed
11.
Huang CL, Liu D, Ishikawa S, Nakashima T, Nakashima N, Yokomise H, Kadota K, Ueno M: Wnt1 overexpression promotes tumour progression in non-small cell lung cancer. EUROPEAN JOURNAL OF CANCER. 2008, 44: 2680-2688. 10.1016/j.ejca.2008.08.004.CrossRefPubMed
12.
de La Coste A, Romagnolo B, Billuart P, Renard CA, Buendia MA, Soubrane O, Fabre M, Chelly J, Beldjord C, Kahn A, Perret C: Somatic mutations of the beta-catenin gene are frequent in mouse and human hepatocellular carcinomas. Proc Natl Acad Sci USA. 1998, 95: 8847-8851. 10.1073/pnas.95.15.8847.CrossRefPubMed
13.
Maiti S, Alam R, Amos CI, Huff V: Frequent association of beta-catenin and WT1 mutations in Wilms tumors. Cancer Res. 2000, 60: 6288-6292.PubMed
14.
Behrens J, Jerchow BA, Würtele M, Grimm J, Asbrand C, Wirtz R, Kühl M, Wedlich D, Birchmeier W: Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science. 1998, 280: 596-599. 10.1126/science.280.5363.596.CrossRefPubMed
15.
Mazieres J, He B, You L, Xu Z, Lee AY, Mikami I, Reguart N, Rosell R, McCormick F, Jablons DM: Wnt inhibitory factor-1 is silenced by promoter hypermethylation in human lung cancer. Cancer Res. 2004, 64: 4717-4720. 10.1158/0008-5472.CAN-04-1389.CrossRefPubMed
16.
Bos CL, Kodach LL, van den Brink GR, Diks SH, van Santen MM, Richel DJ, Peppelenbosch MP, Hardwick JC: Effect of aspirin on the Wnt/beta-catenin pathway is mediated via protein phosphatase 2A. Oncogene. 2006, 25: 6447-6456. 10.1038/sj.onc.1209658.CrossRefPubMed
17.
Nath N, Kashfi K, Chen J, Rigas B: Nitric oxide-donating aspirin inhibits beta-catenin/T cell factor (TCF) signaling in SW480 colon cancer cells by disrupting the nuclear beta-catenin-TCF association. Proc Natl Acad Sci USA. 2003, 100: 12584-12589. 10.1073/pnas.2134840100.PubMedCentralCrossRefPubMed
18.
Park Hoon Chi, Chang Young Joon, Hahm Ryeong Eun, Park Seyeon, Kim Hyun-Kyung, Yang Hak Chul: Quercetin, a potent inhibitor against β-catenin/Tcf signaling in SW480 colon cancer cells. Biochemical and Biophysical Research Communications. 2005, 328: 227-234. 10.1016/j.bbrc.2004.12.151.CrossRefPubMed
19.
Lepourcelet M, Chen YN, France DS, Wang H, Crews P, Petersen F, Bruseo C, Wood AW, Shivdasani RA: Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex. Cancer Cell. 2004, 5: 91-102. 10.1016/S1535-6108(03)00334-9.CrossRefPubMed
20.
Eguchi M, Nguyen C, Lee SC, Kahn M: ICG-001, a novel small molecule regulator of TCF/beta-catenin transcription. Med Chem. 2005, 1: 467-472. 10.2174/1573406054864098.CrossRefPubMed
21.
He B, Reguart N, You L, Mazieres J, Xu Z, Lee AY, Mikami I, McCormick F, Jablons DM: Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells containing downstream mutations. Oncogene. 2005, 24: 3054-3058. 10.1038/sj.onc.1208511.CrossRefPubMed
22.
You L, He B, Xu Z, Uematsu K, Mazieres J, Fujii N, Mikami I, Reguart N, McIntosh JK, Kashani-Sabet M, McCormick F, Jablons DM: An anti-Wnt-2 monoclonal antibody induces apoptosis in malignant melanoma cells and inhibits tumor growth. Cancer Res. 2004, 64: 5385-5389. 10.1158/0008-5472.CAN-04-1227.CrossRefPubMed
23.
Wright M, Aikawa M, Szeto W, Papkoff J: Identification of a Wnt-responsive signal transduction pathway in primary endothelial cells. Biochem Biophys Res Commun. 1999, 263: 384-388. 10.1006/bbrc.1999.1344.CrossRefPubMed
24.
Monkley SJ, Delaney SJ, Pennisi DJ, Christiansen JH, Wainwright BJ: Targeted disruption of the Wnt2 gene results in placentation defects. Development. 1996, 122: 3343-3353.PubMed
25.
Ishikawa T, Tamai Y, Zorn AM, Yoshida H, Seldin MF, Nishikawa S, Taketo MM: Mouse Wnt receptor gene Fzd5 is essential for yolk sac and placental angiogenesis. Development. 2001, 128: 25-33.PubMed
26.
Mao C, Malek OT, Pueyo ME, Steg PG, Soubrier F: Differential expression of rat frizzled-related frzb-1 and frizzled receptor fz1 and fz2 genes in the rat aorta after balloon injury. Arterioscler Thromb Vasc Biol. 2000, 20: 43-51.CrossRefPubMed
27.
Sala CF, Formenti E, Terstappen GC, Caricasole A: Identification, gene structure, and expression of human frizzled-3 (FZD3). Biochem Biophys Res Commun. 2000, 273: 27-34. 10.1006/bbrc.2000.2882.CrossRefPubMed
28.
Eberhart CG, Argani P: Wnt signaling in human development: Beta-catenin nuclear translocation in fetal lung, kidney, placenta, capillaries, adrenal, and cartilage. Pediatr Dev Pathol. 2001, 4: 351-357. 10.1007/s10024001-0037-y.CrossRefPubMed
29.
Ne'stor T, Masckaucha'n H, Shawber Carrie, Funahashi Yasuhiro, Li Chi-Ming, Kitajewski Jan: Wnt/β-catenin signaling induces proliferation, survival and Interleukin-8 in human endothelial cells. Angiogenesis. 2005, 8: 43-51. 10.1007/s10456-005-5612-9.CrossRef
30.
Yano H, Hara A, Shinoda J, Takenaka K, Yoshimi N, Mori H, Sakai N: Immunohistochemical analysis of beta-catenin in N-ethyl-N-nitrosourea-induced rat gliomas: Implications in regulation ofangiogenesis. Neurol Res. 2000, 22: 527-532.PubMed
31.
Eberhart CG, Tihan T, Burger PC: Nuclear localization and mutation of beta-catenin in medulloblastomas. J Neuropathol Exp Neurol. 2000, 59: 333-337.PubMed
32.
Yano H, Hara A, Takenaka K, Shinoda J, Shimokawa K, Yoshimi N, Mori H, Sakai N: Differential expression of beta-catenin in human glioblastoma multiforme and normal brain tissue. Neurol Res. 2000, 22: 650-656.PubMed
33.
Huang C, Liu D, Masuya D, Nakashima T, Kameyama K, Ishikawa S, Ueno M, Haba R, Yokomise H: Clinical application of biological markers for treatments of resectable non-small-cell lung cancers. Br J Cancer. 2005, 92: 1231-1239. 10.1038/sj.bjc.6602481.PubMedCentralCrossRefPubMed
34.
Gratzinger D, Zhao S, Marinelli RJ, Kapp AV, Tibshirani RJ, Hammer AS, Hamilton-Dutoit S, Natkunam Y: Microvessel Density and Expression of Vascular Endothelial Growth Factor and Its Receptors in Diffuse Large B-Cell Lymphoma Subtypes. The American Journal of Pathology. 2007, 170: 1362-1369. 10.2353/ajpath.2007.060901.PubMedCentralCrossRefPubMed
35.
Zhang X, Gaspard JP, Chung DC: Regulation of vascular endothelial growth factor by the Wnt and K-ras pathways in colonic neoplasia. Cancer Res. 2001, 61: 6050-6054.PubMed
36.
Easwaran V, Lee SH, Inge L, Guo L, Goldbeck C, Garrett E, Wiesmann M, Garcia PD, Fuller JH, Chan V, Randazzo F, Gundel R, Warren RS, Escobedo J, Aukerman SL, Taylor RN, Fantl WJ: beta-Catenin regulates vascular endothelial growth factor expression in colon cancer. Cancer Res. 2003, 63: 3145-3153.PubMed
37.
Huang D, Du X: Crosstalk between tumor cells and microenvironment via wnt pathway in colorectal cancer dissemination. World J Gastroenterol. 2008, 14: 1823-1827. 10.3748/wjg.14.1823.PubMedCentralCrossRefPubMed
38.
Hu J, Dong A, Fernandez-Ruiz V, Shan J, Kawa M, Martínez-Ansó E, Prieto J, Qian C: Blockade of Wnt signaling inhibits angiogenesis and tumor growth in hepatocellular carcinoma. Cancer Res. 2009, 69: 6951-6959. 10.1158/0008-5472.CAN-09-0541.CrossRefPubMed
39.
Reya T, Duncan AW, Ailles L, Domen J, Scherer DC, Willert K, Hintz L, Nusse R, Weissman IL: A role for Wnt signalling in self-renewal of haematopoietic stem cells. Nature. 2003, 423: 409-414. 10.1038/nature01593.CrossRefPubMed
40.
Van Den Berg David, Sharma Arun, Bruno Edward, Hoffman Ron: Role of Members of the Wnt Gene Family in Human Hematopoiesis. Blood. 1998, 92: 3189-3202.PubMed
41.
Brandon C, Eisenberg LM, Eisenberg CA: WNT signaling modulates the diversification of hematopoietic cells. Blood. 2000, 96: 4132-4141.PubMed
42.
Luis TC, Weerkamp F, Naber BA, Baert MR, de Haas EF, Nikolic T, Heuvelmans S, De Krijger RR, van Dongen JJ, Staal FJ: Wnt3a deficiency irreversibly impairs hematopoietic stem cell self-renewal and leads to defects in progenitor cell differentiation. Blood. 2009, 113: 546-554. 10.1182/blood-2008-06-163774.CrossRefPubMed
43.
Reya T, O'Riordan M, Okamura R, Devaney E, Willert K, Nusse R, Grosschedl R: Wnt signaling regulates B lymphocyte proliferation through a LEF-1 dependent mechanism. Immunity. 2000, 13: 15-24. 10.1016/S1074-7613(00)00004-2.CrossRefPubMed
44.
Baba Y, Yokota T, Spits H, Garrett KP, Hayashi S, Kincade PW: Constitutively active beta-catenin promotes expansion of multipotent hematopoietic progenitors in culture. J. Immunol. 2006, 177: 2294-2303.CrossRefPubMed
45.
Ranheim Erik, Kwan Helen, Reya Tannishtha, Wang Yu-Ker, Weissman Irving, Francke Uta: Frizzled 9 knock-out mice have abnormal B-cell development. Blood. 2005, 105: 2487-2494. 10.1182/blood-2004-06-2334.CrossRefPubMed
46.
Staal FJ, Meeldijk J, Moerer P, Jay P, van de Weerdt BC, Vainio S, Nolan GP, Clevers H: Wnt signaling is required for thymocyte development and activates Tcf-1 mediated transcription. Eur J Immunol. 2001, 31: 285-293. 10.1002/1521-4141(200101)31:1<285::AID-IMMU285>3.0.CO;2-D.CrossRefPubMed
47.
Gattinoni L, Zhong XS, Palmer DC, Ji Y, Hinrichs CS, Yu Z, Wrzesinski C, Boni A, Cassard L, Garvin LM, Paulos CM, Muranski P, Restifo NP: Wnt signaling arrests effector T cell differentiation and generates CD8+memory stem cells. Nat Med. 2009, 15: 808-813. 10.1038/nm.1982.PubMedCentralCrossRefPubMed
48.
Baba Y, Garrett KP, Kincade PW: Constitutively active beta-catenin confers multilineage differentiation potential on lymphoid and myeloid progenitors. Immunity. 2005, 23: 599-609. 10.1016/j.immuni.2005.10.009.PubMedCentralCrossRefPubMed
49.
Weerkamp F, van Dongen JJ, Staal FJ: Notch and Wnt signaling in T-lymphocyte development and acute lymphoblastic leukemia. Leukemia. 2006, 20: 1197-1205. 10.1038/sj.leu.2404255.CrossRefPubMed
50.
Khan NI, Bradstock KF, Bendall LJ: Activation of Wnt/beta-catenin pathway mediates growth and survival in B-cell progenitor acute lymphoblastic leukaemia. Br J Haematol. 2007, 138: 338-348. 10.1111/j.1365-2141.2007.06667.x.CrossRefPubMed
51.
Valencia A, Román-Gómez J, Cervera J, Such E, Barragán E, Bolufer P, Moscardó F, Sanz GF, Sanz MA: Wnt signaling pathway is epigenetically regulated by methylation of Wnt antagonists in acute myeloid leukemia. Leukemia. 2009, 23: 1658-1666. 10.1038/leu.2009.86.CrossRefPubMed
52.
Jost E, Schmid J, Wilop S, Schubert C, Suzuki H, Herman JG, Osieka R, Galm O: Epigenetic inactivation of secreted Frizzled-related proteins in acute myeloid leukaemia. Br J Haematol. 2008, 142: 745-753. 10.1111/j.1365-2141.2008.07242.x.CrossRefPubMed
53.
Minke KS, Staib P, Puetter A, Gehrke I, Gandhirajan RK, Schlösser A, Schmitt EK, Hallek M, Kreuzer KA: Small molecule inhibitors of WNT signaling effectively induce apoptosis in acute myeloid leukemia cells. Eur J Haematol. 2009, 82: 165-175. 10.1111/j.1600-0609.2008.01188.x.CrossRefPubMed
54.
Sercan Z, Pehlivan M, Gokturk D, Sercan HO: Beta-catenin mutations are not observed in chronic myeloid leukemia. Tumori. 2009, 95: 836-839.PubMed
55.
Lu D, Zhao Y, Tawatao R, Cottam HB, Sen M, Leoni LM, Kipps TJ, Corr M, Carson DA: Activation of the Wnt signaling pathway in chronic lymphocytic leukemia. PNAS. 2004, 101: 3118-3123. 10.1073/pnas.0308648100.PubMedCentralCrossRefPubMed
56.
Wu QL, Zierold C, Ranheim EA: Dysregulation of Frizzled 6 is a critical component of B-cell leukemogenesis in a mouse model of chronic lymphocytic leukemia. Blood. 2009, 113: 3031-3039. 10.1182/blood-2008-06-163303.PubMedCentralCrossRefPubMed
57.
Everly DN, Kusano S, Raab-Traub N: Accumulation of cytoplasmic beta-catenin and nuclear glycogen synthase kinase 3beta in Epstein-Barr virus-infected cells. J Virol. 2004, 78: 11648-11655. 10.1128/JVI.78.21.11648-11655.2004.PubMedCentralCrossRefPubMed
58.
Dutta-Simmons J, Zhang Y, Gorgun G, Gatt M, Mani M, Hideshima T, Takada K, Carlson NE, Carrasco DE, Tai YT, Raje N, Letai AG, Anderson KC, Carrasco DR: Aurora kinase A is a target of Wnt/beta-catenin involved in multiple myeloma disease progression. Blood. 2009, 114: 2699-2708.CrossRefPubMed
59.
Ashihara E, Kawata E, Nakagawa Y, Shimazaski C, Kuroda J, Taniguchi K, Uchiyama H, Tanaka R, Yokota A, Takeuchi M, Kamitsuji Y, Inaba T, Taniwaki M, Kimura S, Maekawa T: beta-catenin small interfering RNA successfully suppressed progression of multiple myeloma in a mouse model. Clin Cancer Res. 2009, 15: 2731-2738. 10.1158/1078-0432.CCR-08-1350.CrossRefPubMed
60.
Gelebart P, Anand M, Armanious H, Peters AC, Dien Bard J, Amin HM, Lai R: Constitutive activation of the Wnt canonical pathway in mantle cell lymphoma. Blood. 2008, 112: 5171-5179. 10.1182/blood-2008-02-139212.PubMedCentralCrossRefPubMed
61.
Chung R, Peters AC, Armanious H, Anand M, Gelebart P, Lai R: Biological and clinical significance of GSK-3beta in mantle cell lymphoma--an immunohistochemical study. Int J Clin Exp Pathol. 2010, 3: 244-253.PubMedCentralPubMed
62.
Bellei Barbara, Pacchiarotti Alberto, Perez Marie, Faraggiana Tullio: Frequent b-catenin overexpression without exon 3 mutation in cutaneous lymphomas. Modern Pathology. 2004, 17: 1275-1281. 10.1038/modpathol.3800181.CrossRefPubMed
63.
Zhang D, O'neil MF, Cunningham MT, Fan F, Olyaee M, Li L: Abnormal Wnt signaling and stem cell activation in reactive lymphoid tissue and low-grade marginal zone lymphoma. Leuk Lymphoma. 2010, 51: 906-910. 10.3109/10428191003695645.CrossRefPubMed
64.
Schmidt Matthias, Sievers Elisabeth, Endo Tomoyuki, Desheng Lu, Carson Dennis, Schmidt-Wolf Ingo: Targeting Wnt pathway in lymphoma and myeloma cells. British Journal of Haematology. 2008, 144: 796-798. 10.1111/j.1365-2141.2008.07503.x.CrossRefPubMed
65.
Kawahara T, Kawaguchi-Ihara N, Okuhashi Y, Itoh M, Nara N, Tohda S: Cyclopamine and quercetin suppress the growth of leukemia and lymphoma cells. Anticancer Res. 2009, 29: 4629-4632.PubMed
Metadata
Title
Role of Wnt canonical pathway in hematological malignancies
Authors
Xueling GE
Xin Wang
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Journal of Hematology & Oncology / Issue 1/2010
Electronic ISSN: 1756-8722
DOI
https://doi.org/10.1186/1756-8722-3-33

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