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.
A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and β-catenin module scores.
ALDH1A1(high) expression or β-catenin(c) expression alone was associated with lymph node metastasis, and worse clinical outcome in breast cancer patients, especially in patients receiving cyclophosphamide treatment.
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.
An analysis of breast cancer patients led us to identify c-Myb as an activator of Wnt/β-catenin signaling. c-Myb interacted with the intracellular Wnt effector β-catenin and coactivated the Wnt/β-catenin target genes Cyclin D1 and Axin2 Moreover, c-Myb controlled metastasis in an Axin2-dependent manner.
Aryl hydrocarbon receptor/cytochrome P450 1A1 pathway mediates breast cancer stem cells expansion through PTEN inhibition and β-Catenin and Akt activation.
Based on the statistical analyses, we speculated that reduced expression of APC leads to overexpression of beta-catenin, and aberrant expression of cyclin D1 and c-myc mainly depends on alterations in the Wnt signaling pathway in breast cancer.
By using human clinical specimens, we also showed that miR-152 expression levels were negatively correlated with β-catenin and PKM2 levels in breast cancer tissues.
Collectively, our findings indicate that elevated FBP1 is a critical modulator in breast cancer progression by altering glucose metabolism and the activity of Wnt/β-Catenin pathway.
Collectively, these data indicate that Wnt/beta-catenin activation is an important feature of basal-like breast cancers and is predictive of worse overall survival, suggesting that it may be an attractive pharmacological target for this aggressive breast cancer subtype.