β-catenin will possibly serve as a potential therapeutic target for patients with triple-negative breast cancer through further understanding the role of Wnt/β-catenin pathway activation.
Additionally, correlation was evaluated between the expression of C-myc and β-catenin to provide the theoretical basis for the targeted therapy of TNBC.
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.
Eventually, the hub genes SRC, EGFR, JUN, CTNNB1, and MYC were derived using distinct topological parameters such as degree, betweenness centrality, closeness centrality, and clustering coefficient, which implicated a central role in 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.
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.
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.
Luteolin suppresses the metastasis of triple-negative breast cancer by reversing epithelial-to-mesenchymal transition via downregulation of β-catenin expression.
Our findings suggested that circRNA_069718 promoted TNBC progression via Wnt/β-catenin pathway and could serve as a novel therapeutic target for TNBC treatment.
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.
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.