Mesenchymal-epithelial transition and AXL inhibitor TP-0903 sensitise triple-negative breast cancer cells to the antimalarial compound, artesunate.

ABSTRACT: Triple-negative breast cancer (TNBC) is a difficult-to-treat, aggressive cancer type. TNBC is often associated with the cellular program of epithelial-mesenchymal transition (EMT) that confers drug resistance and metastasis. EMT and reverse mesenchymal-epithelial transition (MET) programs are regulated by several signaling pathways which converge on a group of transcription factors, EMT- TFs. Therapy approaches could rely on the EMT reversal to sensitise mesenchymal tumours to compounds effective against epithelial cancers. Here, we show that the antimalarial ROS-generating compound artesunate (ART) exhibits higher cytotoxicity in epithelial than mesenchymal breast cancer cell lines. Ectopic expression of EMT-TF ZEB1 in epithelial or ZEB1 depletion in mesenchymal cells, respectively, reduc

SUBMITTER: Terragno M 

PROVIDER: S-EPMC10764797 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature