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

ABSTRACT: 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 3? (GSK3?). 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.

SUBMITTER: Xu LZ

PROVIDER: S-EPMC4202139 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other

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

Xu Ling-Zhi LZ Long Zi-Jie ZJ Peng Fei F Liu Yang Y Xu Jie J Wang Chang C Jiang Lei L Guo Tao T Kamran Muhammad M Li Si-Si SS Wang Chun-Li CL Wang Hong-Jiang HJ Zhao Yong-Fu YF Wan Xian-Yao XY Liu Quentin Q

Oncotarget 20140901 17

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 med ...[more]

PMID: 25115395

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Dataset Information

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

Publications

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

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