KIF14 Promotes AKT Phosphorylation and Contributes to Chemoresistance in Triple-Negative Breast Cancer

摘要: Abstract Despite evidence that kinesin family member 14 (KIF14) can serve as a prognostic biomarker in various solid tumors, how it contributes to tumorigenesis remains unclear. We observed experimental decrease KIF14 expression increases docetaxel chemosensitivity estrogen receptor–negative/progesterone receptor–negative/human epidermal growth factor receptor 2-negative, "triple-negative" breast cancers (TNBC). To investigate the oncogenic role of , we used noncancerous human mammary epithelial cells and ectopically expressed found increased proliferative capacity, anchorage-independent grown vitro resistance but not doxorubicin, carboplatin, or gemcitabine. Seventeen benign biopsies BRCA1 BRCA2 mutation carriers showed mRNA by fluorescence situ hybridization compared controls with no known mutations suggesting high-risk tissue. Evaluation 34 cases locally advanced TNBC significantly correlates chemotherapy-resistant cancer. knockdown also decreased AKT phosphorylation activity. Live-cell imaging confirmed an insulin-induced temporal colocalization at plasma membrane, potential promoting activation AKT. An small-molecule inhibitor was then evaluate anticancer benefits downregulating Inhibition shows chemosensitizing effect decreasing Together, these findings show early critical for tumorigenic TNBC, therapeutic targeting is feasible effective TNBC.