Journal
NATURE COMMUNICATIONS
Volume 4, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms3610
Keywords
-
Categories
Funding
- Hartmut Hoffmann-Berling International Graduate School (HBIGS)
- BMBF [NGFN-Plus 01GS08183, NGFN-plus 01GS08181-6]
- Bavarian genome research network (BayGene)
- ERC
- DFG Collaborative Research Center 873
- DFG [KFO 227]
- Baden-Wurttemberg Stiftung
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available