KIF11 is required for proliferation and self-renewal of docetaxel resistant triple negative breast cancer cells
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Meng Jiang1,2,*, Huiru Zhuang3,*, Rui Xia1,2, Lei Gan1,2, Yuantao Wu1,2, Junzhe Ma1,2, Yihui Sun4 and Zhixiang Zhuang1,2
1Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
2Institute of Radiotherapy and Oncology, Soochow University, Suzhou, 215004, China
3Department of Plastic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
4Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China
*These authors have contributed equally to this work
Zhixiang Zhuang, email: [email protected]
Yihui Sun, email: [email protected]
Keywords: triple negative breast cancer, cancer stem cell, docetaxel resistance, kinesin family member 11
Received: July 18, 2017 Accepted: August 09, 2017 Published: September 08, 2017
Development of chemoresistance remains a major hurdle for triple negative breast cancer treatment. Previous studies suggest that CD44+/CD24- cells, subpopulation of cancer stem cells with self-renewing and tumor-initiating capacities, are partly responsible for chemoresistance and therapeutic failure of triple negative breast cancer. Therefore, novel agents that target cancer stem cells (CSCs) may improve the clinical outcome. KIF11 (kinesin family member 11), overexpressed in many cancer cells, is a molecular motor protein that plays essential role in mitosis. In this study, 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 a significant decrease in the percentage of CSCs and mammosphere formation. KIF11 knockdown also inhibits cell growth and induces cell cycle G2/M arrest followed by cell mitosis and apoptosis. Further docetaxel resistant TNBC xenograft models demonstrated that KIF11 inhibitor exerts growth inhibitory effect in vivo. Of note, we also found that KIF11 was highly expressed in TNBC and its expression was correlated with shorter disease free survival time. All these data indicate that KIF11 is critical for proliferation and self-renewal in TNBC tumor cells in vitro and in vivo, suggesting that KIF11 may be a promising therapeutic target for treating chemoresistant TNBC.
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