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

O Voloshanenko, G Erdmann, TD Dubash… - Nature …, 2013 - nature.com
O Voloshanenko, G Erdmann, TD Dubash, I Augustin, M Metzig, G Moffa, C Hundsrucker…
Nature communications, 2013nature.com
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 …
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.
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