{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T17:50:49Z","timestamp":1774115449866,"version":"3.50.1"},"reference-count":31,"publisher":"Proceedings of the National Academy of Sciences","issue":"28","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,7,15]]},"abstract":"<jats:p>\n            The Wnt family of secreted proteins coordinate cell fate decision-making in a broad range of developmental and homeostatic contexts. Corruption of Wnt signal transduction pathways frequently results in degenerative diseases and cancer. We have used an iterative genome-wide screening strategy that employs multiple nonredundant RNAi reagents to identify mammalian genes that participate in Wnt\/\u03b2-catenin pathway response. Among the genes that were assigned high confidence scores are two members of the TCF\/LEF family of DNA-binding proteins that control the transcriptional output of the pathway. Surprisingly, we found that the presumed cancer-promoting gene\n            <jats:italic>TCF7L2<\/jats:italic>\n            functions instead as a transcriptional repressor that restricts colorectal cancer (CRC) cell growth. Mutations in\n            <jats:italic>TCF7L2<\/jats:italic>\n            identified from cancer genome sequencing efforts abolish its ability to function as a transcriptional regulator and result in increased CRC cell growth. We describe a growth-promoting transcriptional program that is likely activated in CRC tumors with compromised\n            <jats:italic>TCF7L2<\/jats:italic>\n            function. Taken together, the results from our screen and studies focused on members of the TCF\/LEF gene family refine our understanding of how aberrant Wnt pathway activation sustains CRC growth.\n          <\/jats:p>","DOI":"10.1073\/pnas.0804709105","type":"journal-article","created":{"date-parts":[[2008,7,11]],"date-time":"2008-07-11T01:30:37Z","timestamp":1215739837000},"page":"9697-9702","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":150,"title":["A genome-wide RNAi screen for Wnt\/\u03b2-catenin pathway components identifies unexpected roles for TCF transcription factors in cancer"],"prefix":"10.1073","volume":"105","author":[{"given":"Wei","family":"Tang","sequence":"first","affiliation":[{"name":"Departments of *Cell Biology and"}]},{"given":"Michael","family":"Dodge","sequence":"additional","affiliation":[{"name":"Departments of *Cell Biology and"}]},{"given":"Deepika","family":"Gundapaneni","sequence":"additional","affiliation":[{"name":"Departments of *Cell Biology and"}]},{"given":"Carolyn","family":"Michnoff","sequence":"additional","affiliation":[{"name":"Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390"}]},{"given":"Michael","family":"Roth","sequence":"additional","affiliation":[{"name":"Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390"}]},{"given":"Lawrence","family":"Lum","sequence":"additional","affiliation":[{"name":"Departments of *Cell Biology and"}]}],"member":"341","published-online":{"date-parts":[[2008,7,15]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.10.018"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.20.010403.113126"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03319"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/1270"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81333-1"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1133427"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1784"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.275.5307.1787"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01014-0"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1025858928620"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05697"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05179"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109374"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602696200"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.082240999"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.285.5435.1923"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1145720"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/79859"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0501-53"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210056"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.02132-06"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203287"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.08.039"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209859"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1144090"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1143578"},{"key":"e_1_3_3_27_2","volume-title":"Cancer Facts and Figures 2006","year":"2006","unstructured":"Cancer Facts and Figures 2006 (American Cancer Society, Atlanta, GAAvailable at www.cancer.org\/downloads\/STT\/CAFF2006PWSecured.pdf. (2006)."},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2006.07.007"},{"key":"e_1_3_3_29_2","first-page":"919","article-title":"A homologue of the Drosophila headcase protein is a novel tumor marker for early-stage colorectal cancer","volume":"15","author":"Chien CC","year":"2006","unstructured":"CC Chien, CC Chang, SH Yang, SH Chen, CJ Huang, A homologue of the Drosophila headcase protein is a novel tumor marker for early-stage colorectal cancer. Oncol Rep 15, 919\u2013926 (2006).","journal-title":"Oncol Rep"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209470"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.10.042"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0804709105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T22:05:18Z","timestamp":1649801118000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0804709105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,15]]},"references-count":31,"journal-issue":{"issue":"28","published-print":{"date-parts":[[2008,7,15]]}},"alternative-id":["10.1073\/pnas.0804709105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0804709105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7,15]]},"assertion":[{"value":"2008-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-07-15","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}