KIF11 Is Required For Docetaxel Resistant Triple Negative Breast Cancer Cells

Development of chemoresistance remains a major hurdle for triple negative breastcancer treatment.Previous studies suggest that CD44+/CD24-cells,subpopulationof cancer stem cells with self-renewing and tumor-initiating capacities,are partlyresponsible for chemoresistance and therapeutic failure of triple negative breastcancer.Therefore,novel agents that target cancer stem cells(CSCs)may improvethe clinical outcome.KIF11(kinesin family member 11),overexpressed in manycancer cells,is a molecular motor protein that plays essential role in mitosis.In thisstudy,we assess its role in docetaxel resistant triple negative breast cancer(TNBC).We found that the expression of KIF11 was significantly increased in CD44+/CD24-subpopulation of docetaxel resistant TNBC cells.Knockdown of KIF11 resulted in asignificant decrease in the percentage of CSCs and mammosphere formation.KIF11 knockdown also inhibits cell growth and induces cell cycle G2/M arrest followedby cell mitosis and apoptosis.Further docetaxel resistant TNBC xenograft modelsdemonstrated that KIF11 inhibitor exerts growth inhibitory effect in vivo.Of note,wealso found that KIF11 was highly expressed in TNBC and its expression was correlatedwith shorter disease free survival time.All these data indicate that KIF11 is criticalfor proliferation and self-renewal in TNBC tumor cells in vitro and in vivo,suggestingthat KIF11 may be a promising therapeutic target for treating chemoresistant TNBC.