These findings indicate that MUC1 CT plays a role in the intracellular signaling through its interaction with beta-catenin and upregulate the Wnt target gene cyclinD1 in CagA H. pylori-infected gastric carcinoma.
To explore the contribution of AXIN1, AXIN2 and beta-catenin, components of Wnt signaling pathway, to the carcinogenesis of gastric cancer (GC), we examined AXIN1, AXIN2 exon7 and CTNNB1 (encoding beta-catenin) exon3 mutations in 70 GCs.
Attenuation of beta-catenin by shRNA resulted in suppressed cell proliferation and apparent apoptosis, suggesting that beta-catenin may be a target for therapy of gastric cancer.
Together, these findings provide compelling evidence for a deficiency in cell-to-cell adhesion being sufficient to initiate diffuse gastric cancer in the absence of hyperproliferation and beta-catenin activation.
The presumptive causative genetic alterations leading to delocalization of beta-catenin in ICs are still controversial, and there are only a few reports regarding beta-catenin expression in gastric cancer based on mucin phenotypes.
We investigated cell cycle regulators (p53, p21, Rb), APC, beta-catenin and NF-kappaB using immunohistochemistry and EBV using in situ hybridisation for EBV encoded small RNAs in 117 cases of gastric carcinoma.
CD44 up regulation was significantly associated with tyrosine-phosphorylated β-catenin (χ(2) = 22.5; P < 0.001), and this change was closely associated with nuclear translocation of β-catenin (χ(2) = 13.393; P < 0.001) in CagA H. pylori-infected gastric carcinoma.
ERα overexpression effectively inhibited cell growth and cancer progression by suppressing β-catenin in gastric cancer, identifying ERα as a promising target with therapeutic potential for development of new approaches to treat gastric cancer.
Furthermore, the overexpression of Egr-1 upregulated β-catenin expression level, promoted cell proliferation, increased cell population in S-phase and enhanced gastric cancer cell migration and invasion in vitro.
The high expression of marginal KPNA2 was significantly associated with β-catenin accumulation in the nucleus and poor prognosis in two independent GC cohorts (discovery cohort, n = 90, P = 0.018; validation cohort, n = 89, P = 0.0125).
In the present study, we investigated whether caudatin has therapeutic value in gastric cancer and examined the effects of caudatin on the expression of β-catenin in human gastric carcinoma cell lines.
Our results highlight that expression of a Wnt/β-catenin responsive gene ANLN in GC is a molecular predictor of intestinal and proliferative type gastric tumors.