Lovastatin Inhibits EMT and Metastasis of Triple-Negative Breast Cancer Stem Cells Through Dysregulation of Cytoskeleton-Associated Proteins

Triple-negative breast cancer (TNBC) is more aggressive and has poorer prognosis compared to other subtypes of cancer. Epithelial-to-mesenchymal transition (EMT) a process in which epithelial cells transform into mesenchymal-like capable migration, invasion, metastasis. Recently, we have demonstrated that lovastatin, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lipid-lowering drug, could inhibit stemness properties stem (CSCs) derived from TNBC cell vitro vivo . This study aimed at investigating whether lovastatin inhibits CSCs by inhibiting EMT suppressing metastasis the mechanism involved. In present study, found dysregulated lysine succinylation cytoskeleton-associated proteins MDA-MB-231 cell. Lovastatin inhibited as down-regulation protein levels Vimentin Twist reversal TGF-β1-induced morphological change MCF10A cells. also migration CSCs. The disruption cytoskeleton was reduction number pseudopodia relocation F-actin cytoskeleton. Combination with doxorubicin synergistically liver Bioinformatics analysis revealed higher expression genes were characteristic predicted survival outcomes patients. These data suggested through dysregulation proteins.