Overall, accumulation of cytoplasmic β-catenin and downregulation of other Wnt pathway proteins (APC/Axin/DKK3/FRP2/WIF1) were found in approximately half of the breast cancers (47%) in our cohort.
Sustained CDX2 expression was associated with a higher expression of cytoplasmic/membranous β-catenin and with nuclear APC expression (P=0.042 and P<0.01, respectively).
Our study highlights an important scaffolding function of β-catenin in the assembly of the destruction complex and suggests Wnt-inhibited APC-Axin interaction as a mechanism of Wnt-dependent inhibition of the destruction complex.
Removal of the epigenetic markers led to an increase in APC levels and a reduction of β‑catenin expression in two transcriptional targets of the Wnt pathway: Matrix metalloproteinase‑7 and vascular endothelial growth factor.
Western blot analysis was used to detect the effects of si-HOTAIR on multidrug resistance proteins, multidrug resistance-associated protein 1 (MRP1) and multidrug resistance 1 (MDR1), and Wnt signaling pathways, Wnt3a, adenomatous polyposis coli (APC) and β-catenin.
Adenomatous polyposis coli (APC) is a large protein with multiple binding partners, suggesting diverse functions besides its well-known role in the destruction of β-catenin.
Silencing of lncNEN885 could dramatically increase the phosphorylation of glycogen synthase kinase-3β and decrease the expression of adenomatous polyposis coli and Axin, with the subsequent accumulation of β-catenin.
Familial adenomatous polyposis patients develop d-FGPs earlier and more often develop additional ones than non-syndromic patients. d-FGPs in FAP and non-syndromic patients have similar low rates of β-catenin nuclear IHC positivity.
Colon cancers frequently bear inactivating mutations of the adenomatous polyposis coli (<i>APC</i>) gene, whose product is an important component of the destruction complex that regulates β-catenin levels.
These results reveal that APC-regulated β-catenin activity in cortical progenitors sets the appropriate Wnt tone necessary for normal cerebral cortical development.
In this work, we concurrently deleted Smad4 and the tumor suppressor and endogenous Wnt/beta-catenin inhibitor adenomatous polyposis coli (Apc) in luminal prostate cells in mice.
Most sporadic DTs are associated with β-catenin gene (CTNNB1) mutations, while mutated APC gene causes FAP disease. microRNAs (miRNAs) are involved in many human carcinogenesis.The miRNA profile was analyzed by microarray in formalin-fixed, paraffin-embedded (FFPE) specimens of 12 patients (8 sporadic, 4 FAP-associated) and 4 healthy controls.
The mRNA and protein levels of β‑catenin, c‑myc and survivin were significantly reduced in SW480/APC‑Axin cells when compared with the SW480/APC group.
CAF-derived WNT2 activated canonical signaling in adenomatous polyposis coli/β-catenin wild-type colon cancer cells in a paracrine fashion, whereas no hyperactivation was detectable in cell lines harboring mutations in the adenomatous polyposis coli/β-catenin pathway.
PrxII deletion in mice with inactivating mutation of adenomatous polyposis coli (APC) gene reduces intestinal adenomatous polyposis via Axin/β-catenin axis and thereby promotes survival.
Inhibitors of the Wingless-related Integration site (WNT)/β-catenin pathway have recently been under consideration as potential chemopreventive agents against Familial Adenomatous Polyposis (FAP).
IHC assay or Western blotting showed that EESB decreased protein expression of β-catenin, c-Myc and Survivin, as well as increased APC expression and β-catenin phosphorylation in tumor tissues or HT-29 cells (P<0.05).
Mechanistically, we found that MALAT1 activated the Wnt/β‑catenin pathway by inhibiting the expression of Axin1 and adenomatous polyposis coli (APC), and subsequently promoting the expression of cyclin D1.
Lidocaine had no specific effect on cell cycle but increased by 10× the mRNA level of adenomatous polyposis coli (P < .01), which acts as an antagonist of the Wnt/β-catenin pathway.
However, activating mutations in β-catenin, Axin and Adenomatous Polyposis Coli only contribute to a portion of the Wnt signaling hyper-activation observed in hepatocellular carcinoma.
We calculate that an activating mutation in one allele near the critical GSK3β phosphorylation site on β-catenin is >10<sup>5</sup>-times more likely to produce CRC by random mutagenesis due to chemicals than inactivating two alleles in APC, yet it does not occur in humans.
Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the β-catenin degradation complex, minimized the suppressive effect of H2 on β-catenin accumulation.