{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:14:43Z","timestamp":1791238483785,"version":"4.1.0"},"reference-count":39,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T00:00:00Z","timestamp":1288569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Oncogene"],"published-print":{"date-parts":[[2011,2,24]]},"DOI":"10.1038\/onc.2010.475","type":"journal-article","created":{"date-parts":[[2010,11,1]],"date-time":"2010-11-01T15:01:20Z","timestamp":1288623680000},"page":"956-966","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Diverse mechanisms of Wnt activation and effects of pathway inhibition on proliferation of human gastric carcinoma cells"],"prefix":"10.1038","volume":"30","author":[{"given":"S","family":"Asciutti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Akiri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Grumolato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Vijayakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S A","family":"Aaronson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,11,1]]},"reference":[{"key":"BFonc2010475_CR1","doi-asserted-by":"publisher","first-page":"2163","DOI":"10.1038\/onc.2009.82","volume":"28","author":"G Akiri","year":"2009","unstructured":"Akiri G, Cherian MM, Vijayakumar S, Liu G, Bafico A, Aaronson SA . (2009). Wnt pathway aberrations including autocrine Wnt activation occur at high frequency in human non-small-cell lung carcinoma. Oncogene 28: 2163\u20132172.","journal-title":"Oncogene"},{"key":"BFonc2010475_CR2","doi-asserted-by":"publisher","first-page":"27489","DOI":"10.1074\/jbc.270.46.27489","volume":"270","author":"DR Alessi","year":"1995","unstructured":"Alessi DR, Cuenda A, Cohen P, Dudley DT, Saltiel AR . (1995). PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. J Biol Chem 270: 27489\u201327494.","journal-title":"J Biol Chem"},{"key":"BFonc2010475_CR3","doi-asserted-by":"publisher","first-page":"2819","DOI":"10.1038\/sj.onc.1201797","volume":"16","author":"A Bafico","year":"1998","unstructured":"Bafico A, Gazit A, Wu-Morgan SS, Yaniv A, Aaronson SA . (1998). Characterization of Wnt-1 and Wnt-2-induced growth alterations and signaling pathways in NIH3T3 fibroblasts. Oncogene 16: 2819\u20132825.","journal-title":"Oncogene"},{"key":"BFonc2010475_CR4","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1002\/(SICI)1097-0215(20000515)86:4<533::AID-IJC15>3.0.CO;2-O","volume":"86","author":"PLW Bas","year":"2000","unstructured":"Bas PLW, Friedel N, Nico JDB, Hugo WT, Winand NMD . (2000). Genetic alterations involving exon 3 of the \u03b2-catenin gene do not play a role in adenocarcinomas of the esophagus. Int J Cancer 86: 533\u2013537.","journal-title":"Int J Cancer"},{"key":"BFonc2010475_CR5","doi-asserted-by":"publisher","first-page":"2092","DOI":"10.1128\/MCB.01405-08","volume":"29","author":"M Bechard","year":"2009","unstructured":"Bechard M, Dalton S . (2009). Subcellular localization of glycogen synthase kinase 3-\u03b2 controls embryonic stem cell self-renewal. Mol Cell Biol 29: 2092\u20132104.","journal-title":"Mol Cell Biol"},{"key":"BFonc2010475_CR6","first-page":"369","volume":"10","author":"K Caca","year":"1999","unstructured":"Caca K, Kolligs FT, Ji X, Hayes M, Qian J, Yahanda A et al. (1999). \u03b2- and \u03b3-catenin mutations, but not E-cadherin inactivation, underlie T-cell factor\/lymphoid enhancer factor transcriptional deregulation in gastric and pancreatic cancer. Cell Growth Differ 10: 369\u2013376.","journal-title":"Cell Growth Differ"},{"key":"BFonc2010475_CR7","first-page":"3503","volume":"62","author":"WM Clements","year":"2002","unstructured":"Clements WM, Wang J, Sarnaik A, Kim OJ, MacDonald J, Fenoglio-Preiser C et al. (2002). \u03b2-catenin mutation is a frequent cause of Wnt pathway activation in gastric cancer. Cancer Res 62: 3503\u20133506.","journal-title":"Cancer Res"},{"key":"BFonc2010475_CR8","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1038\/84691","volume":"7","author":"CM D'Cruz","year":"2001","unstructured":"D'Cruz CM, Gunther EJ, Boxer RB, Hartman JL, Sintasath L, Moody SE et al. (2001). c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat Med 7: 235\u2013239.","journal-title":"Nat Med"},{"key":"BFonc2010475_CR9","doi-asserted-by":"publisher","first-page":"33398","DOI":"10.1074\/jbc.M107977200","volume":"277","author":"M Filali","year":"2002","unstructured":"Filali M, Cheng N, Abbott D, Leontiev V, Engelhardt JF . (2002). Wnt-3A\/\u03b2-catenin signaling induces transcription from the LEF-1 promoter. J Biol Chem 277: 33398\u201333410.","journal-title":"J Biol Chem"},{"key":"BFonc2010475_CR10","doi-asserted-by":"publisher","first-page":"1394","DOI":"10.1136\/gut.34.10.1394","volume":"34","author":"FM Giardiello","year":"1993","unstructured":"Giardiello FM, Offerhaus GJ, Lee DH, Krush AJ, Tersmette AC, Booker SV et al. (1993). Increased risk of thyroid and pancreatic carcinoma in familial adenomatous polyposis. Gut 34: 1394\u20131396.","journal-title":"Gut"},{"key":"BFonc2010475_CR11","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1046\/j.1365-2559.2001.01177.x","volume":"39","author":"H Grabsch","year":"2001","unstructured":"Grabsch H, Takeno S, Noguchi T, Hommel G, Gabbert HE, Mueller W . (2001). Different patterns of \u03b2-catenin expression in gastric carcinomas: relationship with clinicopathological parameters and prognostic outcome. Histopathology 39: 141\u2013149.","journal-title":"Histopathology"},{"key":"BFonc2010475_CR12","doi-asserted-by":"publisher","first-page":"1509","DOI":"10.1126\/science.281.5382.1509","volume":"281","author":"T-C He","year":"1998","unstructured":"He T-C, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT et al. (1998). Identification of c-MYC as a target of the APC pathway. Science 281: 1509\u20131512.","journal-title":"Science"},{"key":"BFonc2010475_CR13","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1111\/j.1349-7006.2002.tb01226.x","volume":"93","author":"T Ikenoue","year":"2002","unstructured":"Ikenoue T, Ijichi H, Kato N, Kanai F, Masaki T, Rengifo W et al. (2002). Analysis of the \u03b2-catenin\/T-cell factor signaling pathway in 36 gastrointestinal and liver cancer cells. Jpn J Cancer Res 93: 1213\u20131220.","journal-title":"Jpn J Cancer Res"},{"key":"BFonc2010475_CR14","doi-asserted-by":"publisher","first-page":"8109","DOI":"10.1128\/MCB.00404-06","volume":"26","author":"JW Jang","year":"2006","unstructured":"Jang JW, Boxer RB, Chodosh LA . (2006). Isoform-specific ras activation and oncogene dependence during MYC- and Wnt-induced mammary tumorigenesis. Mol Cell Biol 26: 8109\u20138121.","journal-title":"Mol Cell Biol"},{"key":"BFonc2010475_CR15","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1053\/j.gastro.2006.08.011","volume":"131","author":"K-P Janssen","year":"2006","unstructured":"Janssen K-P, Alberici P, Fsihi H, Gaspar C, Breukel C, Franken P et al. (2006). APC and oncogenic KRAS are synergistic in enhancing Wnt signaling in intestinal tumor formation and progression. Gastroenterology 131: 1096\u20131109.","journal-title":"Gastroenterology"},{"key":"BFonc2010475_CR16","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1128\/MCB.22.4.1172-1183.2002","volume":"22","author":"EH Jho","year":"2002","unstructured":"Jho EH, Zhang T, Domon C, Joo CK, Freund JN, Costantini F . (2002). Wnt\/\u03b2-catenin\/Tcf signaling induces the transcription of Axin2, a negative regulator of the signaling pathway. Mol Cell Biol 22: 1172\u20131183.","journal-title":"Mol Cell Biol"},{"key":"BFonc2010475_CR17","first-page":"2744","volume":"62","author":"J-S Kim","year":"2002","unstructured":"Kim J-S, Crooks H, Dracheva T, Nishanian TG, Singh B, Jen J et al. (2002). Oncogenic \u03b2-catenin is required for bone morphogenetic protein 4 expression in human cancer cells. Cancer Res 62: 2744\u20132748.","journal-title":"Cancer Res"},{"key":"BFonc2010475_CR18","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.cellsig.2006.08.008","volume":"19","author":"S-E Kim","year":"2007","unstructured":"Kim S-E, Lee W-J, Choi K-Y . (2007). The PI3 kinase-Akt pathway mediates Wnt3a-induced proliferation. Cellular Signal 19: 511\u2013518.","journal-title":"Cellular Signal"},{"key":"BFonc2010475_CR19","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1101\/gad.14.11.1319","volume":"14","author":"FT Kolligs","year":"2000","unstructured":"Kolligs FT, Kolligs B, Hajra KM, Hu G, Tani M, Cho KR et al. (2000). \u03b3-Catenin is regulated by the APC tumor suppressor and its oncogenic activity is distinct from that of \u03b2-catenin. Genes Dev 14: 1319\u20131331.","journal-title":"Genes Dev"},{"issue":"10","key":"BFonc2010475_CR20","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1055\/s-2005-858638","volume":"43","author":"P Michl","year":"2005","unstructured":"Michl P, Downward J . (2005). Mechanisms of disease: PI3K\/AKT signaling in gastrointestinal cancers. Z Gastroenterol, 1133\u20131139.","journal-title":"Zeitschrift f\u00fcr Gastroenterologie"},{"key":"BFonc2010475_CR21","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1126\/science.275.5307.1787","volume":"275","author":"PJ Morin","year":"1997","unstructured":"Morin PJ, Spa rks AB, Korinek V, Barker N, Clevers H, Vogelstein B et al. (1997). Activation of \u03b2-catenin-Tcf signaling in colon cancer by mutations in \u03b2-catenin or APC. Science 275: 1787\u20131790.","journal-title":"Science"},{"key":"BFonc2010475_CR22","first-page":"90","volume":"3","author":"MJ Overman","year":"2009","unstructured":"Overman MJ . (2009). Recent advances in the management of adenocarcinoma of the small intestine. Gastrointest Cancer Res 3: 90\u201396.","journal-title":"Gastrointest Cancer Res"},{"key":"BFonc2010475_CR23","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1242\/jcs.02779","volume":"119","author":"K-S Park","year":"2006","unstructured":"Park K-S, Jeon SH, Kim S-E, Bahk Y-Y, Holmen SL, Williams BO et al. (2006). APC inhibits ERK pathway activation and cellular proliferation induced by RAS. J Cell Sci 119: 819\u2013827.","journal-title":"J Cell Sci"},{"key":"BFonc2010475_CR24","doi-asserted-by":"publisher","first-page":"e45","DOI":"10.1093\/nar\/29.9.e45","volume":"29","author":"MW Pfaffl","year":"2001","unstructured":"Pfaffl MW . (2001). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29: e45.","journal-title":"Nucleic Acids Res"},{"key":"BFonc2010475_CR25","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1073\/pnas.94.2.448","volume":"94","author":"KM Pumiglia","year":"1997","unstructured":"Pumiglia KM, Decker SJ . (1997). Cell cycle arrest mediated by the MEK\/mitogen-activated protein kinase pathway. Proc Natl Acad Sci USA 94: 448\u2013452.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFonc2010475_CR26","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1073\/pnas.86.3.802","volume":"86","author":"JS Rubin","year":"1989","unstructured":"Rubin JS, Osada H, Finch PW, Taylor WG, Rudikoff S, Aaronson SA . (1989). Purification and characterization of a newly identified growth factor specific for epithelial cells. Proc Natl Acad Sci USA 86: 802\u2013806.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFonc2010475_CR27","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1126\/science.275.5307.1790","volume":"275","author":"B Rubinfeld","year":"1997","unstructured":"Rubinfeld B, Robbins P, El-Gamil M, Albert I, Porfiri E, Polakis P . (1997). Stabilization of \u03b2-catenin by genetic defects in melanoma cell lines. Science 275: 1790\u20131792.","journal-title":"Science"},{"key":"BFonc2010475_CR28","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1128\/MCB.02375-06","volume":"28","author":"M Shimizu","year":"2008","unstructured":"Shimizu M, Fukunaga Y, Ikenouchi J, Nagafuchi A . (2008). Defining the roles of \u03b2-catenin and plakoglobin in LEF\/T-cell factor-dependent transcription using \u03b2-catenin\/plakoglobin-null F9 cells. Mol Cell Biol 28: 825\u2013835.","journal-title":"Mol Cell Biol"},{"key":"BFonc2010475_CR29","doi-asserted-by":"publisher","first-page":"723","DOI":"10.1006\/jmcc.1998.0655","volume":"30","author":"BK Slinker","year":"1998","unstructured":"Slinker BK . (1998). The statistics of synergism. J Mol Cell Cardiol 30: 723\u2013731.","journal-title":"J Mol Cell Cardiol"},{"key":"BFonc2010475_CR30","doi-asserted-by":"publisher","first-page":"2394","DOI":"10.1073\/pnas.82.8.2394","volume":"82","author":"MR Stampfer","year":"1985","unstructured":"Stampfer MR, Bartley JC . (1985). Induction of transformation and continuous cell lines from normal human mammary epithelial cells after exposure to benzo[a]pyrene. Proc Natl Acad Sci USA 82: 2394\u20132398.","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFonc2010475_CR31","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1002\/1098-2264(2000)9999:9999<::AID-GCC1097>3.0.CO;2-9","volume":"30","author":"N Sunaga","year":"2001","unstructured":"Sunaga N, Kohno T, Kolligs FT, Fearon ER, Saito R, Yokota J . (2001). Constitutive activation of the Wnt signaling pathway by CTNNB1 (\u03b2-catenin) mutations in a subset of human lung adenocarcinoma. Genes Chromosomes Cancer 30: 316\u2013321.","journal-title":"Genes Chromosomes Cancer"},{"key":"BFonc2010475_CR32","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1002\/gcc.20135","volume":"42","author":"G Suriano","year":"2005","unstructured":"Suriano G, Vrcelj N, Senz J, Ferreira P, Masoudi H, Cox K et al. (2005). \u03b2-Catenin (CTNNB1) gene amplification: a new mechanism of protein overexpression in cancer. Genes Chromosomes Cancer 42: 238\u2013246.","journal-title":"Genes Chromosomes Cancer"},{"key":"BFonc2010475_CR33","doi-asserted-by":"publisher","first-page":"8649","DOI":"10.1128\/MCB.24.19.8649-8661.2004","volume":"24","author":"J Teuliere","year":"2004","unstructured":"Teuliere J, Faraldo MM, Shtutman M, Birchmeier W, Huelsken J, Thiery JP et al. (2004). \u03b2-Catenin-dependent and -independent effects of \u03b4 N-plakoglobin on epidermal growth and differentiation. Mol Cell Biol 24: 8649\u20138661.","journal-title":"Mol Cell Biol"},{"key":"BFonc2010475_CR34","doi-asserted-by":"publisher","first-page":"4079","DOI":"10.1158\/0008-5472.CAN-06-4025","volume":"67","author":"H Tomita","year":"2007","unstructured":"Tomita H, Yamada Y, Oyama T, Hata K, Hirose Y, Hara A et al. (2007). Development of gastric tumors in ApcMin\/+ mice by the activation of the \u03b2-catenin\/Tcf signaling pathway. Cancer Res 67: 4079\u20134087.","journal-title":"Cancer Res"},{"key":"BFonc2010475_CR35","doi-asserted-by":"publisher","first-page":"vi13","DOI":"10.1093\/annonc\/mdl976","volume":"17","author":"E Van Cutsem","year":"2006","unstructured":"Van Cutsem E, Dicato M, Arber N, Benson A, Cunningham D, Diaz-Rubio E et al. (2006). The neo-adjuvant, surgical and adjuvant treatment of gastric adenocarcinoma. Current expert opinion derived from the Seventh World Congress on Gastrointestinal Cancer, Barcelona, 2005. Ann Oncol 17: vi13\u2013vi18.","journal-title":"Ann Oncol"},{"key":"BFonc2010475_CR36","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/S0092-8674(02)01014-0","volume":"111","author":"M van de Wetering","year":"2002","unstructured":"van de Wetering M, Sancho E, Verweij C, de Lau W, Oving I, Hurlstone A et al. (2002). The (\u03b2)-catenin\/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells. Cell 111: 241\u2013250.","journal-title":"Cell"},{"key":"BFonc2010475_CR37","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1016\/S0021-9258(17)37680-9","volume":"269","author":"CJ Vlahos","year":"1994","unstructured":"Vlahos CJ, Matter WF, Hui KY, Brown RF . (1994). A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J Biol Chem 269: 5241\u20135248.","journal-title":"J Biol Chem"},{"key":"BFonc2010475_CR38","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1002\/1097-0215(20010320)95:2<108::AID-IJC1019>3.0.CO;2-#","volume":"95","author":"DK Woo","year":"2001","unstructured":"Woo DK, Kim HS, Lee HS, Kang YH, Yang HK, Kim WH . (2001). Altered expression and mutation of \u03b2-catenin gene in gastric carcinomas and cell lines. Int J Cancer 95: 108\u2013113.","journal-title":"Int J Cancer"},{"key":"BFonc2010475_CR39","doi-asserted-by":"publisher","first-page":"4238","DOI":"10.1128\/MCB.20.12.4238-4252.2000","volume":"20","author":"J Zhurinsky","year":"2000","unstructured":"Zhurinsky J, Shtutman M, Ben-Ze\u2032ev A . (2000). Differential mechanisms of LEF\/TCF family-dependent transcriptional activation by \u03b2-catenin and plakoglobin. Mol Cell Biol 20: 4238\u20134252.","journal-title":"Mol Cell Biol"}],"container-title":["Oncogene"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/onc2010475.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/onc2010475","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/onc2010475.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,21]],"date-time":"2022-03-21T17:17:40Z","timestamp":1647883060000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/onc2010475"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,11,1]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2011,2,24]]}},"alternative-id":["BFonc2010475"],"URL":"https:\/\/doi.org\/10.1038\/onc.2010.475","relation":{},"ISSN":["0950-9232","1476-5594"],"issn-type":[{"value":"0950-9232","type":"print"},{"value":"1476-5594","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,11,1]]},"assertion":[{"value":"17 June 2010","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 August 2010","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2010","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 November 2010","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no conflict of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}