Regulation of Wnt receptor activity: Implications for therapeutic development in colon cancer.
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ABSTRACT:
SUBMITTER: Zhong ZA
PROVIDER: S-EPMC8214085 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Aberrant regulation of the Wnt/?-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 ?-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 ?-catenin, downstream signalling remains responsive to Wnt ligands and receptor proximal signalling. Furthermore, we demonstrate that truncated APC proteins bind ?-catenin and key components of the destruction complex. These results indicate that cells with mutations in APC or ?-catenin depend on Wnt ligands and their secretion for a sufficient level of ?-catenin signalling, which potentially opens new avenues for therapeutic interventions by targeting Wnt secretion via Evi/Wls.
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