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

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Oksana Voloshanenko - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Gerrit Erdmann - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Taronish D. Dubash - , German Cancer Research Center (DKFZ) (Author)
  • Iris Augustin - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Marie Metzig - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Giusi Moffa - , University of Regensburg (Author)
  • Christian Hundsrucker - , University of Regensburg (Author)
  • Grainne Kerr - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Thomas Sandmann - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Benedikt Anchang - , University of Regensburg (Author)
  • Kubilay Demir - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Christina Boehm - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Svenja Leible - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)
  • Claudia R. Ball - , German Cancer Research Center, partner site Dresden, Environmental Monitoring and Endocrinology (Research Group), National Center for Tumor Diseases Dresden, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Consortium (DKTK) partner site Freiburg (Author)
  • Hanno Glimm - , German Cancer Research Center, partner site Dresden, National Center for Tumor Diseases Dresden, National Center for Tumor Diseases (NCT) Heidelberg, German Cancer Consortium (DKTK) partner site Freiburg (Author)
  • Rainer Spang - , University of Regensburg (Author)
  • Michael Boutros - , German Cancer Research Center (DKFZ), Heidelberg University  (Author)

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.

Details

Original languageEnglish
Article number2610
JournalNature communications
Volume4
Publication statusPublished - 2013
Peer-reviewedYes

External IDs

PubMed 24162018