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Targeting of Wnt signaling represents a promising anti-cancer therapy. However, the consequences of systemically attenuating the Wnt pathway in an adult organism are unknown. Here, we globally prevent Wnt secretion by genetically ablating Wntless. We find ...
Aberrantly active Wnt signaling is the hallmark driver of colorectal cancer (CRC). Bcl9/9l proteins are components of the main transcriptional activation complex of canonical Wnt signaling and interact with beta-catenin via a highly conserved homology doma ...
BCL9 and PYGO are beta-catenin cofactors that enhance the transcription of Wnt target genes. They have been proposed as therapeutic targets to diminish Wnt signaling output in intestinal malignancies. Here we find that, in colorectal cancer cells and in de ...
Bcl9 and Bcl9l (Bcl9/9l) encode Wnt signaling components that mediate the interaction between beta-catenin and Pygopus (Pygo) via two evolutionarily conserved domains, HD1 and HD2, respectively. We generated mouse strains lacking these domains to probe the ...
Cold Spring Harbor Laboratory Press2014
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BCL9/9L proteins enhance the transcriptional output of the beta-catenin/TCF transcriptional complex and contribute critically to upholding the high WNT signaling level required for stemness maintenance in the intestinal epithelium. Here we show that a BCL9 ...
Elsevier Science Bv2015
The development of drug resistance, the prime cause of failure in cancer therapy, is commonly explained by the selection of resistant mutant cancer cells. However, dynamic non-genetic heterogeneity of clonal cell populations continuously produces metastabl ...