An identical CTNNB1 mutation was identified in the 1996 liver tumor together with a TERT promoter mutation showing that this hepatocellular carcinoma results from the malignant transformation of the initial β-catenin inflammatory adenoma.
We found that forced overexpression of SKP2, N-RasV12 or ΔN90-β-catenin alone as well as co-expression of SKP2 and ΔN90-β-catenin did not induce liver tumor development.
Fifty percent of the hepatic tumors in these transgenic mice had activating somatic mutations within the beta-catenin gene similar to those found in colon cancers and melanomas.
Overall, while chronic administration of the model CAR activator NaPB results in both hepatocellular adenoma and carcinoma in the low spontaneous liver tumour incidence C57BL/10 J mouse strain, only 40% of the liver tumours evaluated in this study had β-catenin mutations.
We have analysed the role of beta-catenin in the pathogenesis of hepatoblastoma (HB), an embryonic liver tumor occurring mainly in children under 2 years of age.
Our data indicate that beta-catenin can be considered a specific target for gene therapy in pediatric hepatic tumors with mutations and overexpression of this gene.
Overexpression of Tbx3 is closely associated with the mutational status of beta-catenin in murine liver tumors induced by Myc as well as in human hepatocellular carcinomas and hepatoblastomas.
Taken together, these data indicate that β-catenin creates a protumorigenic hepatic environment in part by indirectly activating Nrf2 and implicate oxidative stress as a possible driving force for a subset of β-catenin-driven liver tumors in children.
These data established Wnt/β-catenin as a novel signal produced by infiltrating macrophages induced by steatosis that promotes growth of tumor progenitor cells, underlying the increased risk of liver tumor development in obese individuals.
The cell proliferation was significantly inhibited (up to 95.11 %) by shRNA plus anti-cancer drugs, suggesting that GPC-3 gene should be a potential target for promoting hepatoma cell apoptosis and inhibiting metastasis through the Wnt/β-catenin and Hh singling pathways.
This was confirmed by RT-qPCR of an independent cohort of CTNNB1-mutated HCC and the suppression of the LKB1-related profile upon β-catenin silencing of CTNNB1-mutated human hepatoma cell lines.
Here we show that conductin is upregulated in human tumors that are induced by beta-catenin/Wnt signaling, i.e., high levels of conductin protein and mRNA were found in colorectal and liver tumors but not in the corresponding normal tissues.