Voloshanenko, Oksana and Erdmann, Gerrit and Dubash, Taronish D. and Augustin, Iris and Metzig, Marie and Moffa, Giusi and Hundsrucker, Christian and Kerr, Grainne and Sandmann, Thomas and Anchang, Benedikt and Demir, Kubilay and Boehm, Christina and Leible, Svenja and Ball, Claudia R. and Glimm, Hanno and Spang, Rainer and Boutros, Michael (2013) Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells. NATURE COMMUNICATIONS, 4: 2610. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
Aberrant regulation of the Wnt/beta-catenin pathway has an important role during the onset and progression of colorectal cancer, with over 90% of cases of sporadic colon cancer featuring mutations in APC or beta-catenin. However, it has remained a point of controversy whether these mutations are sufficient to activate the pathway or require additional upstream signals. Here we show that colorectal tumours express elevated levels of Wnt3 and Evi/Wls/GPR177. We found that in colon cancer cells, even in the presence of mutations in APC or beta-catenin, downstream signalling remains responsive to Wnt ligands and receptor proximal signalling. Furthermore, we demonstrate that truncated APC proteins bind beta-catenin and key components of the destruction complex. These results indicate that cells with mutations in APC or beta-catenin depend on Wnt ligands and their secretion for a sufficient level of beta-catenin signalling, which potentially opens new avenues for therapeutic interventions by targeting Wnt secretion via Evi/Wls.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PHOSPHORYLATED BETA-CATENIN; COLORECTAL-CANCER; STEM-CELLS; WNT/BETA-CATENIN; ADENOMATOUS POLYPOSIS; SOMATIC MUTATIONS; SIGNAL-TRANSDUCTION; TRUNCATED APC; IN-VIVO; PROTEIN; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2020 06:22 |
| Last Modified: | 30 Mar 2020 06:22 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15909 |
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