The expression of β-catenin and STT3A/B in colon cancer tissues was initially detected by immunohistochemistry, followed by correlation analyses of the survival rate with the expression of β-catenin and STT3A/B as well as identification of the interaction between β-catenin and STT3A/B.
RNA interference revealed that it controls the level and/or the activity of β-catenin, but it is less efficient and binds less well to β-catenin than APC, thereby providing one explanation as to why the gene is not mutated in colon cancer.
In an in vitro study using a human colon cancer cell line, SW480, inhibition of STAT3 by dominant negative STAT3 or the Janus kinase inhibitor, AG490, induced translocation of beta-catenin from the nucleus to the cytoplasm or membrane.
Depletion of CCAR1 inhibits expression of several Wnt/beta-catenin target genes and suppresses anchorage-independent growth of the colon cancer cell line.
Thus, our data provide a functional definition of the MCR: the APC fragments typical of colon cancer are selected for the presence of a single functional 20R, the first one, and are therefore equivalent relative to beta-catenin binding.
Our findings suggest APC mutations alter regulation of both beta- and gamma-catenin, perhaps explaining why the frequency of APC mutations in colon cancer far exceeds that of beta-catenin mutations.
AFAP1-AS1 knockdown also increased the expression of E-cadherin and ZO-1 while inhibited the expression of Vimentin, MMP9, ZEB1 and β-catenin, suggesting that AFAP1-AS1 is involved in the epithelial-mesenchymal transition (EMT) process of CC.
These results indicate that caffeic acid phenethyl ester is an excellent inhibitor of beta-catenin/T-cell factor signaling in colon cancer cell lines and suggest that caffeic acid phenethyl ester merits further study as an agent against colorectal cancers.
Mutations in components of the Wnt signaling pathway initiate colorectal carcinogenesis by deregulating the beta-catenin transcriptional coactivator. beta-Catenin activation of one target in particular, the c-Myc proto-oncogene, is required for colon cancer pathogenesis. beta-Catenin is known to regulate c-Myc expression via sequences upstream of the transcription start site.
Heterozygous loss of PPARgamma causes an increase in beta-catenin levels and a greater incidence of colon cancer when animals are treated with azoxymethane.
Origin of Somatic Mutations in β-Catenin versus Adenomatous Polyposis Coli in Colon Cancer: Random Mutagenesis in Animal Models versus Nonrandom Mutagenesis in Humans.
These results indicate that the functional antisense oligonucleotides directed against beta-catenin might have potential as a therapeutic intervention to treat colon cancer.
Using genetic approaches, studies in human colon cancers and Drosophila have identified CDK8 as a colon cancer oncogene that regulates beta-catenin transcriptional activity.
To more precisely delineate the role of beta-catenin signaling in colon cancer growth, we treated mice bearing APC-mutant SW480 colon cancer xenografts with antisense oligonucleotides (ODNs) directed against beta-catenin mRNA and examined effects on beta-catenin expression and tumor growth.