Wnt/B- catenin signaling is very active in metastatic breast cancer cells that express a specific gene. Wnt/B catenin signaling is prevalent in breast cancer cells that express micro RNA 374a. The micro RNA 374a directly targets and suppresses the multiple negative regulators of the Wnt-B catenin signaling such as WIF1, PTEN, and WNT5A. The inhibition of B-catenin signaling by the DKK1 or the SFRP1 protein overexpression reduces the expression of breast epithelial markers. An accumulation of B-catenin in the primary tumors further emphasizes the essential role of B-catenin in the process of metastasis. The canonical Wnt/B catenin signaling pathway is initiated when the Wnt ligands bind to its receptors named Frizzled and LDL receptor related protein 5 or 6 (LRP5 or LRP6). The protein disheveled (dvl) is phosphorylated and that allows it to dissociate B-catenin from the destruction complex. The destruction complex is composed of axin, adenomatous polyposis coli (APC), casein kinase la (CKla) and glycogen synthase kinase 3B …show more content…
Wnt/B plays an important role in progression of breast cancer. The mutations in the B-catenin are rare but the localization of b-catenin is abnormal in breast cancer. The data shows that the down regulation of WIF1, PTEN and WNT5A intervenes with the effects of miR374a on B-catenin activation. WIF1 acts as Wnt inhibitor that binds directly to wnt. Because of this binding site the joining of the Wnt ligands to the frizzled receptor is constrained. WIF1 functions as a tumor suppressor and the functional loss of it could spark Wnt/B-catenin signaling and lead to tumor invasion and metastasis. PTEN is also involved in tumor metastasis through B-catenin signaling. PTEN also supplies the suppression of tumor metastasis and reduction of this protein is likely to promote metastasis by enhancing proliferation of cancer cells and inhibiting apoptosis. WNT5A is a protein that doesn’t transform and it is a ligand for noncanonical WNT signaling. The low expression of WNT5A is prevalent in high numbers in patients with breast cancer. Up regulated miR-374a also leads to suppression of multiple inhibitors of B-catenin signaling and the studies show miRNA is activator of the pathway that leads to tumor