The Wnt Signaling Pathway and Its Role in Tumor Development

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2003 Apr 23

PMID 12707770

Citations 191

Authors

B Lustig

J Behrens

Affiliations

Soon will be listed here.

Abstract

Cancer development depends on the aberrant activation of signal transduction pathways that control cell growth and survival and play important roles in normal embryonic development. This review will focus on one of the most powerful pathways, the canonical Wnt signal transduction cascade, which has been originally described in vertebrate and non-vertebrate embryogenesis and subsequently associated with the development of a multitude of different tumor types, mainly of gastrointestinal origin. In recent years, a variety of novel interacting components and functions have been identified in the Wnt pathway revealing not only the complexity of Wnt signaling but also its potency. Here we will concentrate on the role of the Wnt pathway in cancer development with emphasis placed on the molecular defects known to promote neoplastic transformation in humans and in animal models.

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References

Brabletz T, Jung A, Kirchner T . Beta-catenin and the morphogenesis of colorectal cancer. Virchows Arch. 2002; 441(1):1-11. DOI: 10.1007/s00428-002-0642-9. View

Ilyas M, Tomlinson I, Rowan A, Pignatelli M, Bodmer W . Beta-catenin mutations in cell lines established from human colorectal cancers. Proc Natl Acad Sci U S A. 1997; 94(19):10330-4. PMC: 23362. DOI: 10.1073/pnas.94.19.10330. View

Sarris A, Ford R . Recent advances in the molecular pathogenesis of lymphomas. Curr Opin Oncol. 1999; 11(5):351-63. DOI: 10.1097/00001622-199909000-00006. View

Amit S, Hatzubai A, Birman Y, Andersen J, Ben-Shushan E, Mann M . Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. Genes Dev. 2002; 16(9):1066-76. PMC: 186245. DOI: 10.1101/gad.230302. View

Kramps T, Peter O, Brunner E, Nellen D, Froesch B, Chatterjee S . Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell. 2002; 109(1):47-60. DOI: 10.1016/s0092-8674(02)00679-7. View

Watson S, Smith A . Hypergastrinemia promotes adenoma progression in the APC(Min-/+) mouse model of familial adenomatous polyposis. Cancer Res. 2001; 61(2):625-31. View

Martin B, Schneider R, Janetzky S, Waibler Z, Pandur P, Kuhl M . The LIM-only protein FHL2 interacts with beta-catenin and promotes differentiation of mouse myoblasts. J Cell Biol. 2002; 159(1):113-22. PMC: 2173499. DOI: 10.1083/jcb.200202075. View

Hart M, de los Santos R, Albert I, Rubinfeld B, Polakis P . 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):573-81. DOI: 10.1016/s0960-9822(98)70226-x. View

Chung E, Hwang S, Nguyen P, Lee S, Kim J, Kim J . Regulation of leukemic cell adhesion, proliferation, and survival by beta-catenin. Blood. 2002; 100(3):982-90. DOI: 10.1182/blood.v100.3.982. View

10.

Shiina N, Tsukita S . The dynamic behavior of the APC-binding protein EB1 on the distal ends of microtubules. Curr Biol. 2000; 10(14):865-8. DOI: 10.1016/s0960-9822(00)00600-x. View

11.

Kielman M, Rindapaa M, Gaspar C, van Poppel N, Breukel C, van Leeuwen S . Apc modulates embryonic stem-cell differentiation by controlling the dosage of beta-catenin signaling. Nat Genet. 2002; 32(4):594-605. DOI: 10.1038/ng1045. View

12.

Ben-Yedidia T, Shtutman M, Feinstein E, Einat P, Ben-Zeev A . Nr-CAM is a target gene of the beta-catenin/LEF-1 pathway in melanoma and colon cancer and its expression enhances motility and confers tumorigenesis. Genes Dev. 2002; 16(16):2058-72. PMC: 186445. DOI: 10.1101/gad.227502. View

13.

Roose J, Huls G, van Beest M, Moerer P, van der Horn K, Goldschmeding R . Synergy between tumor suppressor APC and the beta-catenin-Tcf4 target Tcf1. Science. 1999; 285(5435):1923-6. DOI: 10.1126/science.285.5435.1923. View

14.

Sekine S, Shibata T, Kokubu A, Morishita Y, Noguchi M, Nakanishi Y . Craniopharyngiomas of adamantinomatous type harbor beta-catenin gene mutations. Am J Pathol. 2002; 161(6):1997-2001. PMC: 1850925. DOI: 10.1016/s0002-9440(10)64477-x. View

15.

Kielhorn E, Provost E, Olsen D, DAquila T, Smith B, Camp R . Tissue microarray-based analysis shows phospho-beta-catenin expression in malignant melanoma is associated with poor outcome. Int J Cancer. 2002; 103(5):652-6. DOI: 10.1002/ijc.10893. View

16.

Verbeek S, Izon D, Hofhuis F, Te Riele H, van de Wetering M, Oosterwegel M . An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature. 1995; 374(6517):70-4. DOI: 10.1038/374070a0. View

17.

Struhl G . Evidence that Armadillo transduces wingless by mediating nuclear export or cytosolic activation of Pangolin. Cell. 2002; 111(2):265-80. DOI: 10.1016/s0092-8674(02)01037-1. View

18.

von Kries J, Winbeck G, Asbrand C, Sochnikova N, DellOro A, Behrens J . Hot spots in beta-catenin for interactions with LEF-1, conductin and APC. Nat Struct Biol. 2000; 7(9):800-7. DOI: 10.1038/79039. View

19.

Yamada Y, Oyama T, Hirose Y, Hara A, Sugie S, Yoshida K . beta-Catenin mutation is selected during malignant transformation in colon carcinogenesis. Carcinogenesis. 2003; 24(1):91-7. DOI: 10.1093/carcin/24.1.91. View

20.

Habas R, Kato Y, He X . Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel Formin homology protein Daam1. Cell. 2002; 107(7):843-54. DOI: 10.1016/s0092-8674(01)00614-6. View