Role of canonical Wnt signaling in endometrial carcinogenesis

Expert Review of Anticancer Therapy

Volumn 12, Issue 1, 2012, Pages 51-62

  Dellinger, Thanh H ^a   Planutis, Kestutis ^b   Tewari, Krishnansu S ^a   Holcombe, Randall F ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

catenin; canonical Wnt signaling; carcinogenesis; endometrial cancer; novel therapeutic targets; Wnt antagonists

Indexed keywords

ACETYLSALICYLIC ACID; APC PROTEIN; AXIN; BETA CATENIN; DICKKOPF 1 PROTEIN; ESTROGEN; LYMPHOID ENHANCER FACTOR 1; MAMMALIAN TARGET OF RAPAMYCIN; NONSTEROID ANTIINFLAMMATORY AGENT; PROGESTERONE; SECRETED FRIZZLED RELATED PROTEIN 1; SEX HORMONE; SONIC HEDGEHOG PROTEIN; T CELL FACTOR PROTEIN; UVOMORULIN; WNT PROTEIN;

CARCINOGENESIS; DRUG MECHANISM; DRUG TARGETING; ENDOMETRIUM CANCER; GENE MUTATION; GENE TARGETING; HUMAN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; REVIEW; SIGNAL TRANSDUCTION;

ANIMALS; CELL TRANSFORMATION, NEOPLASTIC; CLINICAL TRIALS, PHASE II AS TOPIC; DRUG EVALUATION, PRECLINICAL; ENDOMETRIAL NEOPLASMS; FEMALE; HUMANS; WNT PROTEINS; WNT SIGNALING PATHWAY;

EID: 83455236520     PISSN: 14737140     EISSN: 17448328     Source Type: Journal    
DOI: 10.1586/era.11.194     Document Type: Review

References (162)

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics 2010. CA Cancer J. Clin. 60(5), 277-300 (2010).
2. Bokhman JV. Two pathogenetic types of endometrial carcinoma. Gynecol. Oncol. 15(1), 10-17 (1983).
3. Obel JC, Friberg G, Fleming GF. Chemotherapy in endometrial cancer. Clin. Adv. Hematol. Oncol. 4(6), 459-468 (2006).
4. Dellinger TH, Monk BJ. Systemic therapy for recurrent endometrial cancer: a review of North American trials. Expert Rev. Anticancer Ther. 9(7), 905-916 (2009).
5. Oza AM, Elit L, Tsao MS et al. Phase II Study of temsirolimus in women with recurrent or metastatic endometrial cancer: a trial of the NCIC Clinical Trials Group. J. Clin. Oncol. (2011).
6. Aghajanian C, Sill MW, Darcy KM et al. Phase II trial of bevacizumab in recurrent or persistent endometrial cancer: a Gynecologic Oncology Group study. J. Clin. Oncol. 29(16), 2259-2265 (2011).
7. Creasman WT, Boronow RC, Morrow CP, DiSaia PJ, Blessing J. Adenocarcinoma of the endometrium: its metastatic lymph node potential. A preliminary report. Gynecol. Oncol. 4(3), 239-243 (1976).
8. Vogelstein B, Fearon ER, Hamilton SR et al. Genetic alterations during colorectal-tumor development. N. Engl. J. Med. 319(9), 525-532 (1988).
9. Sparks AB, Morin PJ, Vogelstein B, Kinzler KW. Mutational analysis of the APC/beta-catenin/Tcf pathway in colorectal cancer. Cancer Res. 58(6), 1130-1134 (1998).
10. Giles RH, van Es JH, Clevers H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim. Biophys. Acta 1653(1), 1-24 (2003).
11. Fukuchi T, Sakamoto M, Tsuda H, Maruyama K, Nozawa S, Hirohashi S. Beta-catenin mutation in carcinoma of the uterine endometrium. Cancer Res. 58(16), 3526-3528 (1998).
12. Machin P, Catasus L, Pons C, Munoz J, Matias-Guiu X, Prat J. CTNNB1 mutations and beta-catenin expression in endometrial carcinomas. Hum. Pathol. 33(2), 206-212 (2002).
13. Nei H, Saito T, Yamasaki H, Mizumoto H, Ito E, Kudo R. Nuclear localization of beta-catenin in normal and carcinogenic endometrium. Mol. Carcinog. 25(3), 207-218 (1999).
14. Mirabelli-Primdahl L, Gryfe R, Kim H et al. Beta-catenin mutations are specific for colorectal carcinomas with microsatellite instability but occur in endometrial carcinomas irrespective of mutator pathway. Cancer Res. 59(14), 3346-3351 (1999).
15. Ikeda T, Yoshinaga K, Semba S, Kondo E, Ohmori H, Horii A. Mutational analysis of the CTNNB1 (beta-catenin) gene in human endometrial cancer: frequent mutations at codon 34 that cause nuclear accumulation. Oncol. Rep. 7(2), 323-326 (2000).
16. Schlosshauer PW, Pirog EC, Levine RL, Ellenson LH. Mutational analysis of the CTNNB1 and APC genes in uterine endometrioid carcinoma. Mod. Pathol. 13(10), 1066-1071 (2000).
17. Saegusa M, Hashimura M, Yoshida T, Okayasu I. Beta-Catenin mutations and aberrant nuclear expression during endometrial tumorigenesis. Br. J. Cancer 84(2), 209-217 (2001).
18. Saegusa M, Okayasu I. Frequent nuclear beta-catenin accumulation and associated mutations in endometrioid-type endometrial and ovarian carcinomas with squamous differentiation. J. Pathol. 194(1), 59-67 (2001).
19. Moreno-Bueno G, Hardisson D, Sanchez C et al. Abnormalities of the APC/beta-catenin pathway in endometrial cancer. Oncogene 21(52), 7981-7990 (2002).
20. Ashihara K, Saito T, Mizumoto H, Nishimura M, Tanaka R, Kudo R. Mutation of beta-catenin gene in endometrial cancer but not in associated hyperplasia. Med. Electron Microsc. 35(1), 9-15 (2002).
21. Scholten AN, Creutzberg CL, van den Broek LJ, Noordijk EM, Smit VT. Nuclear beta-catenin is a molecular feature of type I endometrial carcinoma. J. Pathol. 201(3), 460-465 (2003).
22. Pijnenborg JM, Kisters N, van Engeland M et al. APC, beta-catenin, and E-cadherin and the development of recurrent endometrial carcinoma. Int. J. Gynecol. Cancer 14(5), 947-956 (2004).
23. Su HY, Lai HC, Lin YW, Chou YC, Liu CY, Yu MH. An epigenetic marker panel for screening and prognostic prediction of ovarian cancer. Int. J. Cancer 124(2), 387-393 (2009).
24. Su HY, Lai HC, Lin YW et al. Epigenetic silencing of SFRP5 is related to malignant phenotype and chemoresistance of ovarian cancer through Wnt signaling pathway. Int. J. Cancer 127(3), 555-567 (2009).
25. Carmon KS, Loose DS. Secreted frizzled-related protein 4 regulates two Wnt7a signaling pathways and inhibits proliferation in endometrial cancer cells. Mol. Cancer Res. 6(6), 1017-1028 (2008).
26. Zi X, Guo Y, Simoneau AR et al. Expression of Frzb/secreted Frizzled-related protein 3, a secreted Wnt antagonist, in human androgen-independent prostate cancer PC-3 cells suppresses tumor growth and cellular invasiveness. Cancer Res. 65(21), 9762-9770 (2005).
27. Hoang BH, Kubo T, Healey JH et al. Dickkopf 3 inhibits invasion and motility of Saos-2 osteosarcoma cells by modulating the Wnt-beta-catenin pathway. Cancer Res. 64(8), 2734-2739 (2004).
28. Aguilera O, Fraga MF, Ballestar E et al. Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer. Oncogene 25(29), 4116-4121 (2006).
29. Barrantes Idel B, Montero-Pedrazuela A, Guadano-Ferraz A et al. Generation and characterization of Dickkopf3 mutant mice. Mol. Cell Biol. 26(6), 2317-2326 (2006).
30. Fong D, Hermann M, Untergasser G et al. Dkk-3 expression in the tumor endothelium: a novel prognostic marker of pancreatic adenocarcinomas. Cancer Sci. 100(8), 1414-1420 (2009).
31. Kawasaki K, Watanabe M, Sakaguchi M et al. REIC/Dkk-3 overexpression downregulates P-glycoprotein in multidrug-resistant MCF7/ADR cells and induces apoptosis in breast cancer. Cancer Gene Ther. 16(1), 65-72 (2009).
32. Lee EJ, Jo M, Rho SB et al. Dkk3, downregulated in cervical cancer, functions as a negative regulator of beta-catenin. Int. J. Cancer 124(2), 287-297 (2009).
33. Tanimoto R, Abarzua F, Sakaguchi M et al. REIC/Dkk-3 as a potential gene therapeutic agent against human testicular cancer. Int. J. Mol. Med. 19(3), 363-368 (2007).
34. Veeck J, Bektas N, Hartmann A et al. Wnt signalling in human breast cancer: expression of the putative Wnt inhibitor Dickkopf-3 (DKK3) is frequently suppressed by promoter hypermethylation in mammary tumours. Breast Cancer Res. 10(5), R82 (2008).
35. Voorzanger-Rousselot N, Goehrig D, Journe F et al. Increased Dickkopf-1 expression in breast cancer bone metastases. Br. J. Cancer 97(7), 964-970 (2007).
36. Yi N, Liao QP, Li T, Xiong Y. Novel expression profiles and invasiveness-related biology function of Dkk1 in endometrial carcinoma. Oncol. Rep. 21(6), 1421-1427 (2009).
37. Yue W, Sun Q, Dacic S et al. Downregulation of Dkk3 activates beta-catenin/TCF-4 signaling in lung cancer. Carcinogenesis 29(1), 84-92 (2008).
38. Huang J, Zhang YL, Teng XM et al. Down-regulation of SFRP1 as a putative tumor suppressor gene can contribute to human hepatocellular carcinoma. BMC Cancer 7, 126 (2007).
39. Veeck J, Niederacher D, An H et al. Aberrant methylation of the Wnt antagonist SFRP1 in breast cancer is associated with unfavourable prognosis. Oncogene 25(24), 3479-3488 (2006).
40. Gauger KJ, Hugh JM, Troester MA, Schneider SS. Down-regulation of sfrp1 in a mammary epithelial cell line promotes the development of a cd44high/cd24low population which is invasive and resistant to anoikis. Cancer Cell Int. 9, 11 (2009).
41. Chung MT, Lai HC, Sytwu HK et al. SFRP1 and SFRP2 suppress the transformation and invasion abilities of cervical cancer cells through Wnt signal pathway. Gynecol. Oncol. 112(3), 646-653 (2009).
42. Chung MT, Sytwu HK, Yan MD et al. Promoter methylation of SFRPs gene family in cervical cancer. Gynecol. Oncol. 112(2), 301-306 (2009).
43. Fukui T, Kondo M, Ito G et al. Transcriptional silencing of secreted frizzled related protein 1 (SFRP 1) by promoter hypermethylation in non-small-cell lung cancer. Oncogene 24(41), 6323-6327 (2005).
44. Kongkham PN, Northcott PA, Croul SE, Smith CA, Taylor MD, Rutka JT. The SFRP family of WNT inhibitors function as novel tumor suppressor genes epigenetically silenced in medulloblastoma. Oncogene 29(20), 3017-3024 (2010).
45. Hrzenjak A, Tippl M, Kremser ML et al. Inverse correlation of secreted frizzled-related protein 4 and beta-catenin expression in endometrial stromal sarcomas. J. Pathol. 204(1), 19-27 (2004).
46. Risinger JI, Maxwell GL, Chandramouli GV et al. Gene expression profiling of microsatellite unstable and microsatellite stable endometrial cancers indicates distinct pathways of aberrant signaling. Cancer Res. 65(12), 5031-5037 (2005).
47. Orford K, Crockett C, Jensen JP, Weissman AM, Byers SW. Serine phosphorylation-regulated ubiquitination and degradation of beta-catenin. J. Biol. Chem. 272(40), 24735-24738 (1997).
48. Nusse R, van Ooyen A, Cox D, Fung YK, Varmus H. Mode of proviral activation of a putative mammary oncogene (int-1) on mouse chromosome 15. Nature 307(5947), 131-136 (1984).
49. 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 31(1), 99-109 (1982).
50. Kuhl M, Sheldahl LC, Park M, Miller JR, Moon RT. The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet. 16(7), 279-283 (2000).
51. Pandur P, Lasche M, Eisenberg LM, Kuhl M. Wnt-11 activation of a non-canonical Wnt signalling pathway is required for cardiogenesis. Nature 418(6898), 636-641 (2002).
52. Huelsken J, Birchmeier W. New aspects of Wnt signaling pathways in higher vertebrates. Curr. Opin. Genet. Dev. 11(5), 547-553 (2001).
53. He X, Saint-Jeannet JP, Wang Y, Nathans J, Dawid I, Varmus H. A member of the Frizzled protein family mediating axis induction by Wnt-5A. Science 275(5306), 1652-1654 (1997).
54. Slusarski DC, Corces VG, Moon RT. Interaction of Wnt and a Frizzled homologue triggers G-protein-linked phosphatidylinositol signalling. Nature 390(6658), 410-413 (1997).
55. Hartmann C, Tabin CJ. Dual roles of Wnt signaling during chondrogenesis in the chicken limb. Development 127(14), 3141-3159 (2000).
56. Medina A, Reintsch W, Steinbeisser H. Xenopus frizzled 7 can act in canonical and non-canonical Wnt signaling pathways: implications on early patterning and morphogenesis. Mech. Dev. 92(2), 227-237 (2000).
57. Mikels AJ, Nusse R. Purified Wnt5a protein activates or inhibits beta-catenin-TCF signaling depending on receptor context. PLoS Biol. 4(4), e115 (2006).
58. Gryfe R, Swallow C, Bapat B, Redston M, Gallinger S, Couture J. Molecular biology of colorectal cancer. Curr. Probl. Cancer 21(5), 233-300 (1997).
59. 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. 24(3), 245-250 (2000).
60. Cao Q, Lu X, Feng YJ. Glycogen synthase kinase-3beta positively regulates the proliferation of human ovarian cancer cells. Cell Res. 16(7), 671-677 (2006).
61. Thompson B, Townsley F, Rosin-Arbesfeld R, Musisi H, Bienz M. A new nuclear component of the Wnt signalling pathway. Nat. Cell Biol. 4(5), 367-373 (2002).
62. Parker DS, Jemison J, Cadigan KM. Pygopus, a nuclear PHD-finger protein required for Wingless signaling in Drosophila. Development 129(11), 2565-2576 (2002).
63. Kramps T, Peter O, Brunner E et al. Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex. Cell 109(1), 47-60 (2002).
64. Townsley FM, Cliffe A, Bienz M. Pygopus and Legless target Armadillo/beta-catenin to the nucleus to enable its transcriptional co-activator function. Nat. Cell Biol. 6(7), 626-633 (2004).
65. Townsley FM, Thompson B, Bienz M. Pygopus residues required for its binding to Legless are critical for transcription and development. J. Biol. Chem. 279(7), 5177-5183 (2004).
66. Morin PJ. Beta-catenin signaling and cancer. Bioessays 21(12), 1021-1030 (1999).
67. Polakis P. The oncogenic activation of beta-catenin. Curr. Opin. Genet. Dev. 9(1), 15-21 (1999).
68. Tao MH, Freudenheim JL. DNA methylation in endometrial cancer. Epigenetics 5(6), 491-498 (2010).
69. Mareel M, Boterberg T, Noe V et al. E-cadherin/catenin/cytoskeleton complex: a regulator of cancer invasion. J. Cell Physiol. 173(2), 271-274 (1997).
70. Singh M, Darcy KM, Brady WE et al. Cadherins, catenins and cell cycle regulators: Impact on survival in a Gynecologic Oncology Group Phase II endometrial cancer trial. Gynecol Oncol 123(2), 320-328 (2011).
71. Shiozaki H, Tahara H, Oka H et al. Expression of immunoreactive E-cadherin adhesion molecules in human cancers. Am. J. Pathol. 139(1), 17-23 (1991).
72. Dellinger T, Planutis K, Gatcliffe T, DiSaia P, Monk B, Holcombe R. Wnt inhibitor expression as a predictor of progression in patients with endometrial carcinoma: a potential role as prognostic biomarker. Gynecol. Oncol. 116 3(Suppl. 1), S86 (2010).
73. Hsieh SY, Hsieh PS, Chiu CT, Chen WY. Dickkopf-3/REIC functions as a suppressor gene of tumor growth. Oncogene 23(57), 9183-9189 (2004).
74. Abarzua F, Sakaguchi M, Takaishi M et al. Adenovirus-mediated overexpression of REIC/Dkk-3 selectively induces apoptosis in human prostate cancer cells through activation of c-Jun-NH2-kinase. Cancer Res. 65(21), 9617-9622 (2005).
75. Kawakami K, Hirata H, Yamamura S et al. Functional significance of Wnt inhibitory factor-1 gene in kidney cancer. Cancer Res. 69(22), 8603-8610 (2009).
76. Kurose K, Sakaguchi M, Nasu Y et al. Decreased expression of REIC/Dkk-3 in human renal clear cell carcinoma. J. Urol. 171(3), 1314-1318 (2004).
77. Jiang T, Huang L, Wang S, Zhang S. Clinical significance of serum Dkk-3 in patients with gynecological cancer. J. Obstet. Gynaecol. Res. 36(4), 769-773 (2010).
78. Jiang T, Wang S, Huang L, Zhang S. Clinical significance of serum DKK-1 in patients with gynecological cancer. Int. J. Gynecol. Cancer 19(7), 1177-1181 (2009).
79. Abu-Jawdeh G, Comella N, Tomita Y et al. Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy. Lab. Invest. 79(4), 439-447 (1999).
80. Di Domenico M, Santoro A, Ricciardi C et al. Epigenetic fingerprint in endometrial carcinogenesis: the hypothesis of a uterine field cancerization. Cancer Biol. Ther. 12(5), 447-457 (2011).
81. He B, Lee AY, Dadfarmay S et al. Secreted frizzled-related protein 4 is silenced by hypermethylation and induces apoptosis in beta-catenin-deficient human mesothelioma cells. Cancer Res. 65(3), 743-748 (2005).
82. Urakami S, Shiina H, Enokida H et al. Wnt antagonist family genes as biomarkers for diagnosis, staging, and prognosis of renal cell carcinoma using tumor and serum DNA. Clin. Cancer Res. 12(23), 6989-6997 (2006).
83. Tetsu O, McCormick F. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398(6726), 422-426 (1999).
84. He TC, Sparks AB, Rago C et al. Identification of c-MYC as a target of the APC pathway. Science 281(5382), 1509-1512 (1998).
85. Yamada T, Takaoka AS, Naishiro Y et al. Transactivation of the multidrug resistance 1 gene by T-cell factor 4/beta-catenin complex in early colorectal carcinogenesis. Cancer Res. 60(17), 4761-4766 (2000).
86. Crawford HC, Fingleton BM, Rudolph-Owen LA et al. The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors. Oncogene 18(18), 2883-2891 (1999).
87. Kolligs FT, Nieman MT, Winer I et al. ITF-2, a downstream target of the Wnt/TCF pathway, is activated in human cancers with beta-catenin defects and promotes neoplastic transformation. Cancer Cell 1(2), 145-155 (2002).
88. Koh TJ, Bulitta CJ, Fleming JV, Dockray GJ, Varro A, Wang TC. Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis. J. Clin. Invest. 106(4), 533-539 (2000).
89. Mann B, Gelos M, Siedow A et al. Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas. Proc. Natl Acad. Sci. USA 96(4), 1603-1608 (1999).
90. Bergman L, Beelen ML, Gallee MP, Hollema H, Benraadt J, van Leeuwen FE. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of liver and endometrial cancer risk following tamoxifen. Lancet 356(9233), 881-887 (2000).
91. Webb PM. Commentary: weight gain, weight loss, and endometrial cancer. Int J. Epidemiol. 35(1), 166-168 (2006).
92. Cardona-Gomez P, Perez M, Avila J, Garcia-Segura LM, Wandosell F. Estradiol inhibits GSK3 and regulates interaction of estrogen receptors, GSK3, and beta-catenin in the hippocampus. Mol. Cell Neurosci. 25(3), 363-373 (2004).
93. Varea O, Arevalo MA, Garrido JJ, Garcia-Segura LM, Wandosell F, Mendez P. Interaction of estrogen receptors with insulin-like growth factor-I and Wnt signaling in the nervous system. Steroids 75(8-9), 565-569 (2009).
94. Wagner S, Weber S, Kleinschmidt MA, Nagata K, Bauer UM. SET-mediated promoter hypoacetylation is a prerequisite for coactivation of the estrogen-responsive pS2 gene by PRMT1. J. Biol. Chem. 281(37), 27242-27250 (2006).
95. Hou X, Tan Y, Li M, Dey SK, Das SK. Canonical Wnt signaling is critical to estrogen-mediated uterine growth. Mol. Endocrinol. 18(12), 3035-3049 (2004).
96. Katayama S, Ashizawa K, Fukuhara T et al. Differential expression patterns of Wnt and beta-catenin/TCF target genes in the uterus of immature female rats exposed to 17alpha-ethynyl estradiol. Toxicol. Sci. 91(2), 419-430 (2006).
97. McCampbell AS, Broaddus RR, Loose DS, Davies PJ. Overexpression of the insulin-like growth factor I receptor and activation of the AKT pathway in hyperplastic endometrium. Clin. Cancer Res. 12(21), 6373-6378 (2006).
98. Rider V, Isuzugawa K, Twarog M et al. Progesterone initiates Wnt-beta-catenin signaling but estradiol is required for nuclear activation and synchronous proliferation of rat uterine stromal cells. J. Endocrinol. 191(3), 537-548 (2006).
99. Thigpen JT, Brady MF, Alvarez RD et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J. Clin. Oncol. 17(6), 1736-1744 (1999).
100. Zaino RJ, Kauderer J, Trimble CL et al. Reproducibility of the diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer 106(4), 804-811 (2006).
101. Yahata T, Fujita K, Aoki Y, Tanaka K. Long-term conservative therapy for endometrial adenocarcinoma in young women. Hum. Reprod. 21(4), 1070-1075 (2006).
102. Kim YB, Holschneider CH, Ghosh K, Nieberg RK, Montz FJ. Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature. Cancer 79(2), 320-327 (1997).
103. Saegusa M, Hamano M, Kuwata T et al. Upregulation and nuclear localization of beta-catenin in endometrial carcinoma in response to progesterone therapy. Cancer Sci. 94(1), 103-111 (2003).
104. Cloke B, Huhtinen K, Fusi L et al. The androgen and progesterone receptors regulate distinct gene networks and cellular functions in decidualizing endometrium. Endocrinology 149(9), 4462-4474 (2008).
105. Satterfield MC, Song G, Hayashi K, Bazer FW, Spencer TE. Progesterone regulation of the endometrial WNT system in the ovine uterus. Reprod. Fertil. Dev. 20(8), 935-946 (2008).
106. Catalano RD, Critchley HO, Heikinheimo O et al. Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol. Hum. Reprod. 13(9), 641-654 (2007).
107. Wang Y, Hanifi-Moghaddam P, Hanekamp EE et al. Progesterone inhibition of Wnt/beta-catenin signaling in normal endometrium and endometrial cancer. Clin. Cancer Res. 15(18), 5784-5793 (2009).
108. Laplante M, Sabatini DM. mTOR signaling at a glance. J. Cell Sci. 122(Pt 20), 3589-3594 (2009).
109. Sabatini DM, Erdjument-Bromage H, Lui M, Tempst P, Snyder SH. RAFT1: a mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 78(1), 35-43 (1994).
110. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell 12(1), 9-22 (2007).
111. Menon S, Manning BD. Common corruption of the mTOR signaling network in human tumors. Oncogene 27(Suppl. 2), S43-S51 (2008).
112. Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat. Rev. Mol. Cell Biol. 10(5), 307-318 (2009).
113. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev. Cell 17(1), 9-26 (2009).
114. Ingham PW, Taylor AM, Nakano Y. Role of the Drosophila patched gene in positional signalling. Nature 353(6340), 184-187 (1991).
115. Lee JJ, von Kessler DP, Parks S, Beachy PA. Secretion and localized transcription suggest a role in positional signaling for products of the segmentation gene Hedgehog. Cell 71(1), 33-50 (1992).
116. Lanske B, Karaplis AC, Lee K et al. PTH/PTHrP receptor in early development and Indian Hedgehog-regulated bone growth. Science 273(5275), 663-666 (1996).
117. Wijgerde M, Ooms M, Hoogerbrugge JW, Grootegoed JA. Hedgehog signaling in mouse ovary: Indian Hedgehog and desert Hedgehog from granulosa cells induce target gene expression in developing theca cells. Endocrinology 146(8), 3558-3566 (2005).
118. Hebrok M, Kim SK, St Jacques B, McMahon AP, Melton DA. Regulation of pancreas development by Hedgehog signaling. Development 127(22), 4905-4913 (2000).
119. Niemann C, Unden AB, Lyle S, Zouboulis Ch C, Toftgard R, Watt FM. Indian Hedgehog and beta-catenin signaling: role in the sebaceous lineage of normal and neoplastic mammalian epidermis. Proc. Natl Acad. Sci. USA 100(Suppl. 1), 11873-11880 (2003).
120. Perron M, Boy S, Amato MA et al. A novel function for Hedgehog signalling in retinal pigment epithelium differentiation. Development 130(8), 1565-1577 (2003).
121. Evangelista M, Tian H, de Sauvage FJ. The Hedgehog signaling pathway in cancer. Clin. Cancer Res. 12(20 Pt 1), 5924-5928 (2006).
122. Liao X, Siu MK, Au CW et al. Aberrant activation of Hedgehog signaling pathway contributes to endometrial carcinogenesis through beta-catenin. Mod. Pathol. 22(6), 839-847 (2009).
123. Barker N, Clevers H. Mining the Wnt pathway for cancer therapeutics. Nat. Rev. Drug Discov. 5(12), 997-1014 (2006).
124. Kim JS, Crooks H, Foxworth A, Waldman T. Proof-of-principle: oncogenic beta-catenin is a valid molecular target for the development of pharmacological inhibitors. Mol. Cancer Ther. 1(14), 1355-1359 (2002).
125. Takahashi-Yanaga F, Sasaguri T. The Wnt/beta-catenin signaling pathway as a target in drug discovery. J. Pharmacol. Sci. 104(4), 293-302 (2007).
126. Maier TJ, Janssen A, Schmidt R, Geisslinger G, Grosch S. Targeting the beta-catenin/APC pathway: a novel mechanism to explain the cyclooxygenase-2- independent anticarcinogenic effects of celecoxib in human colon carcinoma cells. FASEB J. 19(10), 1353-1355 (2005).
127. Dihlmann S, Siermann A, von Knebel Doeberitz M. The nonsteroidal anti-inflammatory drugs aspirin and indomethacin attenuate beta-catenin/TCF-4 signaling. Oncogene 20(5), 645-653 (2001).
128. Baron JA, Cole BF, Sandler RS et al. A randomized trial of aspirin to prevent colorectal adenomas. N. Engl. J. Med. 348(10), 891-899 (2003).
129. Sandler RS, Halabi S, Baron JA et al. A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer. N. Engl. J. Med. 348(10), 883-890 (2003).
130. Thun MJ, Henley SJ, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J. Natl. Cancer Inst. 94(4), 252-266 (2002).
131. Thun MJ, Namboodiri MM, Heath CW Jr. Aspirin use and reduced risk of fatal colon cancer. N. Engl. J. Med. 325(23), 1593-1596 (1991).
132. Chan TA. Nonsteroidal anti-inflammatory drugs, apoptosis, and colon-cancer chemoprevention. Lancet Oncol. 3(3), 166-174 (2002).
133. Giardiello FM, Hamilton SR, Krush AJ et al. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N. Engl. J. Med. 328(18), 1313-1316 (1993).
134. Viswanathan AN, Feskanich D, Schernhammer ES, Hankinson SE. Aspirin, NSAID, and acetaminophen use and the risk of endometrial cancer. Cancer Res. 68(7), 2507-2513 (2008).
135. Bardia A, Ebbert JO, Vierkant RA et al. Association of aspirin and nonaspirin nonsteroidal anti-inflammatory drugs with cancer incidence and mortality. J. Natl Cancer Inst. 99(11), 881-889 (2007).
136. Danforth KN, Gierach GL, Brinton LA et al. Nonsteroidal anti-inflammatory drug use and endometrial cancer risk in the NIH-AARP Diet and Health Study. Cancer Prev. Res. (Phila.) 2(5), 466-472 (2009).
137. Bodelon C, Doherty JA, Chen C, Rossing MA, Weiss NS. Use of nonsteroidal antiinflammatory drugs and risk of endometrial cancer. Am. J. Epidemiol. 170(12), 1512-1517 (2009).
138. Prizment AE, Folsom AR, Anderson KE. Nonsteroidal anti-inflammatory drugs and risk for ovarian and endometrial cancers in the Iowa Women's Health Study. Cancer Epidemiol. Biomarkers Prev. 19(2), 435-442 (2010).
139. Xiaoxin M, Yingnan J, Yanxia L, Shu L, Yuanqi H, Hongwei L. Experimental research on the depressant effect of aspirin on Ishikawa adenocarcinoma endometrium cell growth. Int. J. Gynecol. Cancer 19(7), 1182-1185 (2009).
140. Wood NJ, Quinton NA, Burdall S, Sheridan E, Duffy SR. Exploring the potential chemopreventative effect of aspirin and rofecoxib on hereditary nonpolyposis colorectal cancer-like endometrial cancer cells in vitro through mechanisms involving apoptosis, the cell cycle, and mismatch repair gene expression. Int. J. Gynecol. Cancer 17(2), 447-454 (2007).
141. Hasegawa K, Ohashi Y, Ishikawa K et al. Expression of cyclooxygenase-2 in uterine endometrial cancer and anti-tumor effects of a selective COX-2 inhibitor. Int. J. Oncol. 26(5), 1419-1428 (2005).
142. Gao J, Niwa K, Takemura M et al. Significant anti-proliferation of human endometrial cancer cells by combined treatment with a selective COX-2 inhibitor NS398 and specific MEK inhibitor U0126. Int. J. Oncol. 26(3), 737-744 (2005).
143. Gao J, Niwa K, Sun W et al. Non-steroidal anti-inflammatory drugs inhibit cellular proliferation and upregulate cyclooxygenase-2 protein expression in endometrial cancer cells. Cancer Sci. 95(11), 901-907 (2004).
144. Arango HA, Icely S, Roberts WS, Cavanagh D, Becker JL. Aspirin effects on endometrial cancer cell growth. Obstet. Gynecol. 97(3), 423-427 (2001).
145. Shah S, Hecht A, Pestell R, Byers SW. Trans-repression of beta-catenin activity by nuclear receptors. J. Biol. Chem. 278(48), 48137-48145 (2003).
146. Palmer HG, Gonzalez-Sancho JM, Espada J et al. Vitamin D(3) promotes the differentiation of colon carcinoma cells by the induction of E-cadherin and the inhibition of beta-catenin signaling. J. Cell Biol. 154(2), 369-387 (2001).
147. Park CH, Chang JY, Hahm ER, Park S, Kim HK, Yang CH. Quercetin, a potent inhibitor against beta-catenin/Tcf signaling in SW480 colon cancer cells. Biochem. Biophys. Res. Commun. 328(1), 227-234 (2005).
148. Kim J, Zhang X, Rieger-Christ KM et al. Suppression of Wnt signaling by the green tea compound (-)-epigallocatechin 3-gallate (EGCG) in invasive breast cancer cells. Requirement of the transcriptional repressor HBP1. J. Biol. Chem. 281(16), 10865-10875 (2006).
149. Rao CV, Desai D, Rivenson A, Simi B, Amin S, Reddy BS. Chemoprevention of colon carcinogenesis by phenylethyl-3-methylcaffeate. Cancer Res. 55(11), 2310-2315 (1995).
150. Jaiswal AS, Marlow BP, Gupta N, Narayan S. Beta-catenin-mediated transactivation and cell-cell adhesion pathways are important in curcumin (diferuylmethane)-induced growth arrest and apoptosis in colon cancer cells. Oncogene 21(55), 8414-8427 (2002).
151. Roccaro AM, Leleu X, Sacco A et al. Resveratrol exerts antiproliferative activity and induces apoptosis in Waldenstrom's macroglobulinemia. Clin. Cancer Res. 14(6), 1849-1858 (2008).
152. Gandhirajan RK, Staib PA, Minke K et al. Small molecule inhibitors of Wnt/beta-catenin/lef-1 signaling induces apoptosis in chronic lymphocytic leukemia cells in vitro and in vivo. Neoplasia 12(4), 326-335 (2010).
153. Huang SM, Mishina YM, Liu S et al. Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling. Nature 461(7264), 614-620 (2009).
154. Chen Z, Venkatesan AM, Dehnhardt CM et al. 2,4-diamino-quinazolines as inhibitors of beta-catenin/Tcf-4 pathway: potential treatment for colorectal cancer. Bioorg. Med. Chem. Lett. 19(17), 4980-4983 (2009).
155. Trosset JY, Dalvit C, Knapp S et al. Inhibition of protein-protein interactions: the discovery of druglike beta-catenin inhibitors by combining virtual and biophysical screening. Proteins 64(1), 60-67 (2006).
156. Takahashi-Yanaga F, Kahn M. Targeting Wnt signaling: can we safely eradicate cancer stem cells? Clin. Cancer Res. 16(12), 3153-3162 (2010).
157. You L, He B, Xu Z et al. An anti-Wnt-2 monoclonal antibody induces apoptosis in malignant melanoma cells and inhibits tumor growth. Cancer Res. 64(15), 5385-5389 (2004).
158. Wei W, Chua MS, Grepper S, So SK. Blockade of Wnt-1 signaling leads to anti-tumor effects in hepatocellular carcinoma cells. Mol. Cancer 8, 76 (2009).
159. Tang Y, Simoneau AR, Liao WX et al. WIF1, a Wnt pathway inhibitor, regulates SKP2 and c-myc expression leading to G1 arrest and growth inhibition of human invasive urinary bladder cancer cells. Mol. Cancer Ther. 8(2), 458-468 (2009).
160. He B, You L, Uematsu K et al. A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells. Neoplasia 6(1), 7-14 (2004).
161. DeAlmeida VI, Miao L, Ernst JA, Koeppen H, Polakis P, Rubinfeld B. The soluble wnt receptor Frizzled8CRD-hFc inhibits the growth of teratocarcinomas in vivo. Cancer Res. 67(11), 5371-5379 (2007).
162. The Wnt homepage. www.stanford.edu/group/nusselab/cgi-bin/wnt