Wnt secretion is required to maintain high levels of Wnt activity in colon cancer cells

Oksana Voloshanenko, Gerrit Erdmann, Taronish D. Dubash, Iris Augustin, Marie Metzig, Giusi Moffa, Christian Hundsrucker, Grainne Kerr, Thomas Sandmann, Benedikt Anchang, Kubilay Demir, Christina Boehm, Svenja Leible, Claudia R. Ball, Hanno Glimm, Rainer Spang and Michael Boutros ()
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Oksana Voloshanenko: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim
Gerrit Erdmann: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim
Taronish D. Dubash: National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ)
Iris Augustin: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim
Marie Metzig: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim
Giusi Moffa: Computational Diagnostics Group, Institute for Functional Genomics, University of Regensburg
Christian Hundsrucker: Computational Diagnostics Group, Institute for Functional Genomics, University of Regensburg
Grainne Kerr: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim
Thomas Sandmann: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim
Benedikt Anchang: Computational Diagnostics Group, Institute for Functional Genomics, University of Regensburg
Kubilay Demir: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim
Christina Boehm: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim
Svenja Leible: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim
Claudia R. Ball: National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ)
Hanno Glimm: National Center for Tumor Diseases (NCT), German Cancer Research Center (DKFZ)
Rainer Spang: Computational Diagnostics Group, Institute for Functional Genomics, University of Regensburg
Michael Boutros: German Cancer Research Center (DKFZ), Div. Signalling and Functional Genomics, and Heidelberg University, Dept. Cell and Molecular Biology, Faculty of Medicine Mannheim

Nature Communications, 2013, vol. 4, issue 1, 1-13

Abstract: Abstract Aberrant regulation of the Wnt/β-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 β-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 β-catenin, downstream signalling remains responsive to Wnt ligands and receptor proximal signalling. Furthermore, we demonstrate that truncated APC proteins bind β-catenin and key components of the destruction complex. These results indicate that cells with mutations in APC or β-catenin depend on Wnt ligands and their secretion for a sufficient level of β-catenin signalling, which potentially opens new avenues for therapeutic interventions by targeting Wnt secretion via Evi/Wls.

Date: 2013
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DOI: 10.1038/ncomms3610

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