We also provide evidence that the post-transcriptional activity of cytoplasmic beta-catenin operates under normoxia in basal-like/triple-negative breast cancer cells, where the beta-catenin knockdown suppresses the stem cell phenotype in vitro and tumor growth in vivo.
Immunofluorescence staining of β-catenin in TNBC cell lines showed both nuclear and cytoplasmic localization, indicating activation of Wnt pathway in TNBC cells. iCRT-3 was the most effective compound for inhibiting proliferation and antagonizing Wnt signaling in TNBC cells.
PTE stimulated Fas signaling, which drives EMT by the ERK1/2 and GSK3β/β-catenin pathways, supporting Fas signaling induction involved in EMT regulation.PTE also triggered autophagy in TNBC.
GDC-0941-triggered WNT/beta-catenin pathway activation was observed in MDA-MB-231 and HCC1937 cells, which are TNBC cell lines showing aberrant WNT/beta-catenin activation, and not in SKBR3 and MCF7 cells.
Collectively, these data suggest that β-catenin is required for triple-negative breast cancer development by controlling numerous tumor-associated properties, such as migration, stemness, anchorage-independent growth and chemosensitivity.
TGF-β/p38α and NR4A1 also play essential roles in the induction of epithelial-to-mesenchymal transition (EMT) and induction of β-catenin in TNBC cells, and these TGF-β-induced responses and nuclear export of NR4A1 are blocked by NR4A1 antagonists, the p38 inhibitor SB202190, and kinase-dead [p38(KD)] and dominant-negative [p38(DN)] forms of p38α.
Additionally, correlation was evaluated between the expression of C-myc and β-catenin to provide the theoretical basis for the targeted therapy of TNBC.
Luteolin suppresses the metastasis of triple-negative breast cancer by reversing epithelial-to-mesenchymal transition via downregulation of β-catenin expression.
Pursuant to our previous finding that HDAC8 regulates CSCs in triple-negative breast cancer (TNBC) cells by targeting Notch1 stability, we investigated related pathways and found HDAC3 to be mechanistically linked to CSC homeostasis by increasing β-catenin expression through the Akt/GSK3β pathway.
We also review the aberrant activated signals found in different subgroups of TNBC, including androgen receptor (AR) and PI3K/AKT/mTOR, Notch, Wnt/β-catenin, Hedge-hog, and TGF-β signaling pathways, which play essential roles in multiple development stages of TNBC.
Furthermore, the bexarotene derivatives also showed significant effects in inhibiting TNBC cell proliferation and migration, modulating cancer stem cell markers expressions, as well as limiting the epithelial-mesenchymal transition (EMT) activities of TNBC cell lines in terms of downregulating EMT marker and blocking nuclear translocation of β-catenin.
Our results also revealed that upregulation of AFAP1-AS1 activated Wnt/β-catenin pathway to promote tumorigenesis and cell invasion by increasing the expression of C-myc and epithelial-mesenchymal transition-related molecules in TNBC.
The results showed that emodin inhibited TNBC proliferation and invasion more efficiently than epirubicin when co‑cultured with adipocytes by downregulating the level of CCL5 in adipocyte supernatants; inhibiting the expression level of protein kinase B (AKT); and activating glycogen synthase kinase‑3i (GSK3) and β‑catenin.