ABSTRACT
Triple-negative breast cancer (TNBC) is a highly lethal subtype of breast cancer associated with early relapse and metastasis. Epithelial to mesenchymal transition (EMT) plays pivotal roles in the progression of TNBC, including inducing cancer stem cell (CSC) properties, chemoresistance, tumor metastasis, and recurrence. Abnormally activated YAP/TAZ induces EMT in TNBC, making it a promising target for drug development. Our goal is to identify potential YAP/TAZ inhibitors from naturally derivative molecules and further study its effects on inhibiting EMT and metastasis of TNBC. In the current study, we demonstrate that luteolin significantly inhibits YAP/TAZ activity by promoting YAP/TAZ degradation in TNBC cells. Luteolin treatment leads to a decrease of mesenchymal markers and an increase of epithelial markers in both TNBC cells and TAZ-induced mesenchymal cells. Consistently, luteolin treatment inhibits cell migration in TNBC cells. Additionally, luteolin inhibits tumor growth in mice xenografted with TNBC cells. Collectively, our results support luteolin as a novel YAP/TAZ inhibitor for development as a new agent for the treatment of TNBC.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Antineoplastic Agents/pharmacology , Cell Movement/drug effects , Epithelial-Mesenchymal Transition/drug effects , Luteolin/pharmacology , Trans-Activators/metabolism , Transcription Factors/metabolism , Triple Negative Breast Neoplasms/drug therapy , Adaptor Proteins, Signal Transducing/genetics , Animals , Cell Line, Tumor , Female , Gene Expression Regulation, Neoplastic , Humans , Mice , Mice, Inbred BALB C , Mice, Nude , Neoplasm Invasiveness , Proteolysis , Signal Transduction , Trans-Activators/genetics , Transcription Factors/genetics , Transcriptional Coactivator with PDZ-Binding Motif Proteins , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Tumor Burden/drug effects , YAP-Signaling ProteinsABSTRACT
We explored the effects of microtopography changes from artificial intervention of soil and water conservation (contour reverse-slope terrace, CRT) on tree growth in a degraded woodland on hillslope in water resource area of Songhua dam in Kunming City. The differences of the diameter at breast height (DBH), tree height, new branch increment, and leaf area index (LAI) of dominant tree species in different plots were compared through dynamic monitoring. Then, the causes of differences were analyzed by combining the soil water availability. The results showed that the maximum and mean values of DBH and height of Pinus yunnanensis (dominant species) in contour reverse-slope terrace plot were larger than those in control plot (CK), and the proportion of small-sized and low-dwarf trees in degraded forest community was higher, which indicated that the growth potential of new and seriously degraded forest was stimulated. The annual variation rate of the ave-rage new branch length and diameter of P. yunnanensis in different plots reached 72.4% and 39.1%, respectively. The changes of new branch growth of P. yunnanensis, LAI of plots, and the new branch growth rate were greater in CRT than those in CK. Soil water content was significantly correlated with both the new branch growth and LAI. The ratio of available water in plot (64.2%) was higher than that in CK (54.7%). During the rainy season (from May to September), the available water in CRT existed longer, which was conducive to tree growth and the improvement of plant community structure in degraded woodland.