Inversely, the high frequency of β-catenin mutations could be related to the increased frequency of malignant transformation in hepatocellular carcinoma.
We show that in HCC but not in peritumoral tissue of the same HCC patients, Ln-5, Snail, and Slug are up-regulated, E-cadherin is down-regulated and beta-catenin is translocated into the nuclei.
The results show a modest correlation between diffuse glutamine synthetase immunostaining and exon 3 β-catenin mutations in hepatocellular adenoma and hepatocellular carcinoma with discrepancy rates >50% in both hepatocellular adenoma and hepatocellular carcinoma.
Therefore, our study reveals the evolving nature of β-catenin in HCC to establish it as a compound tumor promoter during the progression of the disease.
MiR-655-3p might functions as a tumor suppressor by directly targeting ADAM10 and indirectly regulating β-catenin pathway in the development of progression of HCC.
These findings unraveled a novel mechanism of c-Myc and Wnt/β-catenin interplay that dictates HCC pathogenesis, and have implications for the potential applicability of miRNA delivery in targeting the newly identified signaling axis and treating metastatic HCCs.
Finally, significant therapeutic benefit of β-catenin knock-down was demonstrated in established HCC tumor xenografts using doxycycline-inducible shRNA system.
The expression levels of CTNNB1 and MMP9 decreased by knocked down XRCC5 which may promote the progression of HCC via the Wnt/β-catenin signaling pathway.
Moreover, exogenous sFRP1 caused significant decrease of β-catenin/T-cell factor-dependent transcription activity.These findings demonstrate that sFRP1 silencing due to promoter hypermethylation is a major event during tumorigenesis. sFRP1 is also a negative modulator of canonical Wnt signaling, which could contribute to metastasis in HCC progression, thus providing a possible therapeutic strategy against HCC.
PRRl1 mRNA expression was found positively correlated with β-catenin (R = 0.5472, P ˂ 0.0001), c-myc (R = 0.5527, P ˂ 0.0001) and cyclinD1 (R = 0.3948, P = 0.0003) in HCC tissues.
Some driver genes are significantly linked to HCC gender (<i>CTNNB1, ALB, TP53</i>, and <i>AXIN1</i>), race (<i>TP53</i> and <i>CDKN2A</i>), and age (<i>RB1</i>) disparities.
The frequency of positivity for β-catenin and GS staining was significantly higher in L-FABP-negative cases of small HCC than in L-FABP-positive cases of small HCC (P = 0.009 and P = 0.000, respectively).
In summary, our study demonstrated that TXNDC12 could activate β-catenin via protein-protein interaction and promote ZEB1-mediated EMT and HCC metastasis.
The polymorphism rs4135385 of CTNNB1 genotype GA was associated with a higher risk for Stage III + IV HCC (modified Union for International Cancer Control) (P = 0.001, OR = 2.238).Genetic polymorphisms in the WNT2 and CTNNB1 genes were closely associated with HCC risk and progression in a Chinese Han population.
Thus alterations in the beta-catenin gene frequently are selected for during liver tumorigenesis and suggest that disregulation of the Wnt-beta-catenin pathway is a major event in the development of HCC in humans and mice.
Activation of the Wnt signaling pathway is frequently observed in hepatocellular carcinoma (HCC), though mutation of three of its components, CTNNB1, AXIN1, and AXIN2, is observed substantially less often.
In the present study, we identified leupaxin, an adaptor protein sharing homology with the focal adhesion protein, as a novel coactivator for β-catenin in human hepatocellular carcinoma (HCC).
Clinicopathological parameters, progression-free survival (PFS) and overall survival (OS) were evaluated to analyze the association of β-catenin expression with prognosis for HCC patients after TACE.
The present results indicate that (1) mutation of exon 3 of the beta-catenin gene can lead to beta-catenin accumulation, although other mechanisms of accumulation may also operate in HCC, and (2) beta-catenin accumulation and mutation of the beta-catenin gene are not early events in hepatocarcinogenesis, and may be associated with the malignant progression of HCC.