Our findings suggest that, in contrast to E-cadherin, mutations of alpha- and beta-catenin do not contribute to the pathogenesis or the diffuse growth patterns of gastric or breast carcinomas.
Here, we report a comprehensive study of the contribution of genetic variation in six genes encoding the beta-catenin destruction complex (APC, AXIN1, AXIN2, CSNK1D, CSNK1E, and GSK3B) to breast cancer using a Mayo Clinic Breast Cancer Case-Control Study.
For this reason, in present study, the alterations (deletion/methylation/mutation/expression) of MCC and CTNNBIP1 were analyzed in BC of Indian patients (N=120) followed by expression/mutation analysis of β-catenin.
Mutations and deletions that result in the stabilization of beta-catenin are frequently found in a number of tumors, including those of the colon, the liver and the ovary, but are less frequently found in breast cancer.
Nuclear localization of β-catenin showed significant association with alterations in the antagonists and was also significantly high in the ER-/PR- BC samples.
Wnt signaling is associated with initiation and progression process in many tumor types, and alterations in β-Catenin explain only a small proportion of aberrant signaling found in breast cancer, indicating that other Wnt signaling components and/or regulators as GSK3β may be involved.
Breast cancer-specific mutations in CK1epsilon inhibit Wnt/beta-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration.
Whereas some oncogenic pathways have high correlations to breast cancer subtype (RAS, CTNNB1, p53, HER1), others have high variability of activity within a specific subtype (MYC, E2F3, SRC), reflecting biology independent of common clinical factors.
Immunohistochemistry (IHC) was performed to assess the prevalence of MAGE-A, vimentin, E-cadherin and β-catenin in breast cancer tissues and correlate them with clinical pathological parameters.
Although mutation of APC or CTNNB1 (beta-catenin) is rare in breast cancer, activation of Wnt signalling is nonetheless thought to play an important role in breast tumorigenesis, and epigenetic silencing of Wnt antagonist genes, including the secreted frizzled-related protein (SFRP) and Dickkopf (DKK) families, has been observed in various tumours.
Taken together, our results suggested that Mn12Ac inhibited the migration, invasion, and epithelial-mesenchymal transition by regulating Wnt/β-catenin and PI3K/AKT signaling pathways in breast cancer.
Overexpression of DVL3 resulted in upregulation of β‑catenin and amplification of breast cancer cell growth, which confirmed that Wnt/β‑catenin activation via DVL3 is associated with breast cancer oncogenesis.
Natural phytochemicals modulate oxidative stress, leptin, integrin, HER2, MAPK, ERK, Wnt/β-catenin and NFκB signaling along with regulating ERα and ERβ, thereby presenting unique opportunities for both primary and combinatorial interventions in BC.
The results indicate that CUL1 knockdown prohibited the metastasis behaviors of breast cancer cells through downregulation (dephosphorylation) of the EMT signaling pathways of EGFR and Akt/GSK3β/β-catenin in breast cancer.
Aryl hydrocarbon receptor/cytochrome P450 1A1 pathway mediates breast cancer stem cells expansion through PTEN inhibition and β-Catenin and Akt activation.
These findings provide a new perspective to counteract the invasive behavior of breast cancer, indicating that blocking PI3K-AKT pathway-dependent β-catenin accumulation may represent a potential therapeutic approach to control breast cancer.
These data delineate a signaling pathway from ErbB2 to Pak to β-catenin that is required for efficient transformation of mammary epithelial cells, and suggest new therapeutic strategies in ErbB2-positive breast cancer.