We detected seven somatic mutations in a portion of exon 3 encoding for the glycogen synthase kinase 3beta phosphorylation consensus region of the beta-catenin gene in 43 gastric cancers.
In addition, we showed that upregulation of HEF1 increased Wnt5a expression and the nuclear translocation of β-catenin, thereby resulting in poor differentiation in GC.
Integration of information on the genetic and epigenetic alterations revealed that the GCs with the CpG island methylator phenotype (CIMP) tended to have mutations of oncogenes, CTNNB1, ERBB2, KRAS, and PIK3CA.
The WNT pathway was activated by mutations of CTNNB1 in 2 GCs and potentially by aberrant methylation of its negative regulators, such as DKK3, NKD1, and SFRP1, in 49 GCs.
LINC01133 inhibits GC progression and metastasis by acting as a ceRNA for miR-106a-3p to regulate APC expression and the Wnt/β-catenin pathway, suggesting that LINC01133 may serve as a potential prognostic biomarker and anti-metastatic therapeutic target for GC.
In conclusion, FOXF2 is a critical tumor suppressor in gastric carcinogenesis whose methylation status serves as an independent prognostic factor for gastric cancer patients.<b>Significance:</b> FOXF2-mediated upregulation of the E3 ligase IRF2BPL drives ubiquitylation and degradation of β-catenin in gastric cancer, blunting Wnt signaling and suppressing carcinogenesis.<i></i>.
These biological factors are often derived from the genetic process, which is thought to represent a crucial step to gastric cancer (DNA copy number changes, microsatellite instability, thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2, COX-2, matrix metalloproteinases, VEGFR and EGFR).
PS-1/γ-secretase cleaves E-cadherin and releases its bound protein partner, β-catenin, from the actin cytoskeleton, thereby allowing it to translocate into the nucleus and to activate the TCF/LEF-1 transcriptional activator, which may promote GC invasion and metastasis.In conclusion, PS-1 promotes invasion and metastasis in GC and may represent a novel prognostic biomarker and potential therapeutic target for GC treatment.
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.
In conclusion, TBL1XR1 contributes to GC tumorigenesis and progression through the activation of the β-catenin/MMP7/EGFR/ERK signalling pathway and may act as a new therapeutic target for GC.
In the first case, in a 73-year-old female, total gastrectomy was performed for a Gastric Cancer (GC) that was proved to be, based on the immunohistochemical features (positivity for mammaglobin and estrogen receptor and negativity for E-cadherin, β-catenin, CD44 and maspin), a metastasis from an invasive lobular carcinoma of the breast, that was later confirmed.
This was supported by the fact that miR-630-mediated suppression of the EMT phenotype was reversed in the presence of the Wnt/β-catenin inhibitor ICG001. miR-630 plays a protective role against gastric cancer by suppressing EMT through activating the Wnt/β-catenin pathway.