Research Papers:

Aurora kinase a suppresses metabolic stress-induced autophagic cell death by activating mTOR signaling in breast cancer cells

Ling-Zhi Xu, Zi-Jie Long, Fei Peng, Yang Liu, Jie Xu, Chang Wang, Lei Jiang, Tao Guo, Muhammad Kamran, Si-Si Li, Chun-Li Wang, Hong-Jiang Wang, Yong-Fu Zhao, Xian-Yao Wan _ and Quentin Liu

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Oncotarget. 2014; 5:7498-7511. https://doi.org/10.18632/oncotarget.2241

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Ling-Zhi Xu1, Zi-Jie Long2,3, Fei Peng1, Yang Liu1, Jie Xu1, Chang Wang1, Lei Jiang1, Tao Guo1, Muhammad Kamran1, Si-Si Li1, Chun-Li Wang1, Hong-Jiang Wang4, Yong-Fu Zhao5, Xian-Yao Wan6 and Quentin Liu1,2,3

1 Institute of Cancer Stem Cell, Dalian Medical University, Dalian, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China

2 Department of Hematology, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

3 Institute of Hematology, Sun Yat-sen University, Guangzhou, China

4 Department of Breast Surgery, the First Affiliated Hospital, Dalian Medical University, Dalian, China

5 Department of Thyroid Surgery, the Second Affiliated Hospital, Dalian Medical University, Dalian, China

6 Department of Critical Care Medicine, the First Affiliated Hospital, Dalian Medical University, Dalian, China


Quentin Liu, email:

Keywords: aurora kinase; metabolic stress; autophagy; cell death; breast cancer

Received: May 21, 2014 Accepted: July 22, 2014 Published: July 22, 2014


Aberrant Aur-A signaling is associated with tumor malignant behaviors. However, its involvement in tumor metabolic stress is not fully elucidated. In the present study, prolonged nutrient deprivation was conducted into breast cancer cells to mimic metabolic stress in tumors. In these cells, autophagy was induced, leading to caspase-independent cell death, which was blocked by either targeted knockdown of autophagic gene ATG5 or autophagy inhibitor 3-Methyladenine (3-MA). Aur-A overexpression mediated resistance to autophagic cell death and promoted breast cancer cells survival when exposed to metabolic stress. Moreover, we provided evidence that Aur-A suppressed autophagy in a kinase-dependent manner. Furthermore, we revealed that Aur-A overexpression enhanced the mammalian target of rapamycin (mTOR) activity under metabolic stress by inhibiting glycogen synthase kinase 3β (GSK3β). Inhibition of mTOR activity by rapamycin sensitized Aur-A-overexpressed breast cancer cells to metabolic stress-induced cell death. Consistently, we presented an inverse correlation between Aur-A expression (high) and autophagic levels (low) in clinical breast cancer samples. In conclusion, our data provided a novel insight into the cyto-protective role of Aur-A against metabolic stress by suppressing autophagic cell death, which might help to develop alternative cell death avenues for breast cancer therapy.

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